TWIST1 (twist homolog 1 (Drosophila))

2009-11-01   Fátima Valdés-Mora , Teresa Gómez del Pulgar , Juan Carlos Lacal 

Garvan Institute of Medical Research, Sydney 2010, New South Wales, Australia (FVM); Centro Nacional de Biotecnologia, C\\\/ Darwin, 3. Campus Cantoblanco, 28049 Madrid, Spain (TGdP, JCL)





This gene can be found on Chromosome 7 at location 7p21.2, position 19,121,616-19,123,820 reverse strand.


The DNA sequence contains 2 exons and the transcript length is 1,669 bp translated to a 202 residues protein.



The 20.9 kDa protein encoded by TWIST1 gene is a highly conserved transcription factor that belongs to the family of basic helix-loop-helix (bHLH) proteins. In vertebrates, it is involved in embryonic development through the regulation of epithelial-mesenchymal transitions (EMT) during neural crest migration, also it regulates mesoderm determination, myogenesis, and morphogenesis (Hebrok et al., 1994; Chen et al., 1995). Additionally, TWIST1 is involved in the negative regulation of cellular determination and in the differentiation of several lineages including myogenesis, osteogenesis (Bialek et al., 2004), and neurogenesis (Soo et al., 2002). Inhibits myogenesis by sequestrating E proteins, avoiding trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. Also represses expression of proinflammatory cytokines such as TNFA and IL1B (Barnes et al., 2009).
Mutations in this gene have been found in patients with Saethre-Chotzen syndrome (Howard et al., 1997).
TWIST1 has been suggested to be oncogenic, contributing to metastasis through its involvement in EMT regulation (Yang et al., 2004). In addition, TWIST1 is overexpressed in multiple tumor types, and it is usually associated with poor prognosis.
In mammals, there are two Twist-like proteins, TWIST1 and TWIST2 that share high structural homology (Li et al., 1995; Wolf et al., 1991). It is thought that during osteoblast development TWIST2 or Dermo1 may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype [provided by RefSeq]. Interestingly, TWIST2 has a pro-oncogenic role in human cancer (Ansieau et al., 2008).
TWIST1 protein contains a helix-loop-helix DNA-binding domain. Efficient DNA binding requires dimerization with another bHLH protein.
Atlas Image
(Mod Base provided)


The strongest expression of the mRNA is in placental tissue. In adults, mesoderm-derived tissues express TWIST1 mRNA preferentially.




Role in embryonic development
The Twist gene was originally identified as being required for mesoderm induction in Drosophila (Thisse et al., 1987; Leptin et al., 1990) which expression is induced by an interleukin-1-like TOLL receptor through nuclear factor kappaB activation (Furlong et al., 2001).
In vertebrates, Twist is predominantly expressed in neural crest cell where is essential for correct patterning of the neural tube (Chen and Behringer, 1995; Soo et al., 2002). However, the nuclear factor kappaB pathway is not involved in mesoderm formation or neural crest development in vertebrates. Instead, BMP-, Wnt-, and fibroblast growth factor-activated pathways are known to modulate vertebrate neural crest development (Meulemans et al., 2004).
During mesoderm formation in Drosophila, Twist induces the expression of the transcription factor Snail to allow invagination and mesoderm differentiation (Leptin and Grunewald, 1990). During neural crest development in vertebrates, expression of Snail and Slug occurs at the neural plate border where Twist is also expressed, and all three transcription factors play critical roles in neural crest formation (Meulemans and Bronner-Fraser, 2004).
Additional evidence supports the key role of Twist in development, since Twist mutation in mice causes failure in cranial neural tube closure, indicating its role in proper migration and differentiation of neural crest and head mesenchymal cells (Chen and Behringer, 1995; Soo et al., 2002).
Role in myogenesis
TWIST1 functionally inhibits muscle development by sequestrating E proteins from forming functional myogenic complexes with the skeletal muscle specific bHLH factor, MyoD. The mechanism of action is through the block of both cis- and trans- MyoD elements, and inhibiting transactivation of Mef2 (Barnes and Firulli, 2009).
Role in EMT
EMT is a process whereby epithelial cell layers lose polarity and cell-cell contacts and undergo a dramatic remodelling of the cytoskeleton. EMT is essential for the morphogenic movements underlying gastrulation and the subsequent formation of various tissues and organs such as the neural crest, heart, musculoskeletal system, craniofacial structures, and peripheral nervous system, and is also implicated in tissue repair in the adult.
TWIST1 induces EMT through repression of E-cadherin (Yang et al., 2004). Cells undergoing EMT acquire expression of mesenchymal components and manifest a migratory phenotype. TWIST1 triggers the acquisition of invasive properties through induction of pro-migratory molecules, such as the cell adhesion protein N-cadherin (Alexander et al., 2006) and RhoC, as consequence of inducing the microRNA molecule miR-10b (Ma et al., 2007).
Role in control of apoptosis
Twist, as a basic helix-loop-helix transcription factor, may activate or suppress diverse downstream targets, including apoptosis genes. Two studies reported that the expression of Twist could inhibit Myc-induced apoptosis in mouse embryo fibroblasts (Maestro et al., 1999) and neuroblastoma cells (Valsesia-Wittmann et al., 2004). This transcriptional control is relevant during EMT, since Twist may need to activate antiapoptotic programs in order to allow epithelial cells to convert to a mesenchymal fate while avoiding cell death due to loss of cell-cell adhesions by epithelial cells.
Role in cancer
TWIST1 has a key role during cancer development and progression in multiple tumour types. There are four main different malignant processes where this transcription factor is involved: EMT (Vernon et al., 2004), resistance to apoptosis by cytotoxic drugs (Wang et al., 2004) and pro-survival signalling (Puisieux et al., 2006) and hypoxia (Yang et al., 2008).



Germline mutations in the coding region of TWIST1 gene in humans cause Saethre-Chotzen syndrome (SCS), an autosomal-dominant hereditary disorder characterized by limb abnormalities, facial dysmorphisms, and premature fusion of cranial sutures (Howard et al., 1997). This disease is also known as acrocephalosyndactyly type 3 (ACS3).
A frameshift mutation in TWIST1 that produce defects of this protein is the cause of Robinow-Sorauf syndrome (RSS); also known as craniosynostosis-bifid hallux syndrome. RSS is an autosomal dominant defect characterized by minor skull and limb anomalies which is very similar to Saethre-Chotzen syndrome (Kunz et al., 1999).
Missense mutations in the TWIST1 have been found in a significant number of patients of craniosynostosis type 1 (CRS1). Craniosynostosis consists of premature fusion of one or more cranial sutures, resulting in an abnormal head shape (Seto et al., 2007).

Implicated in

Entity name
Breast cancer
In human breast cancer, TWIST1 is overexpressed at protein and mRNA levels (Watanabe et al., 2004; Yang et al., 2004; Martin et al., 2005). This upregulation has been usually associated with malignant features of the tumour: invasive lobular carcinoma, a highly infiltrating tumor type (Yang et al., 2004; Vesuna et al., 2008); the increasing nodal involvement (tumor-node-metastasis status); and the poor prognosis of the patients (Martin et al., 2005). TWIST1 overexpression, as a marker of EMT, has been also associated with the metastasis process. Circulating tumour cells of metastactic breast cancer patients showed an increased in EMT and tumor stem markers, included TWIST1 (Aktas et al., 2009); In addition, micrometastatic cells detected in the bone marrow which have prognostic significance in breast cancer displayed a specific expression of TWIST1 (Watson et al., 2007).
There are a wide number a molecular mechanisms described to explain the oncogenic role of TWIST1 in breast cancer progression. One of the most common is through the inhibition of expression of the epithelial marker E-cadherin (Yang et al., 2004; Vesuna et al., 2008). Recently, it has been reported that the microRNA, miR10b, is transcriptionally regulated by TWIST further leading to the activation of the pro-metastasic gene product RHOC promoting tumor invasion and migration in breast cancer (Ma et al., 2007). TWIST1 prosurvival and proinvasive functions are also mediated by the transcriptional up-regulation of AKT2 (Cheng et al., 2007). Moreover, there is a correlation between Wnt signalling and TWIST1 (Howe et al., 2003), which were included in a poor prognosis gene signature during metastasis to lung (DiMeo et al., 2009). In addition, TWIST1 is able to increased vascular endothelial growth factor (VEGF) synthesis in MCF7 cells inducing angiogenesis and chromosomal instability (Mironchik et al., 2005; Vesuna et al., 2006).
TWIST1 expression is also associated with multidrug resistance since its depletion completely blocked the mesenchymal transformation, partially reversed multidrug resistant and greatly abolished invasion induced by Adriamycin treatment in MCF7 cells (Li et al., 2009). Moreover, TWIST1 specific expression is found in therapy resistant cell populations (Watson et al., 2007; Aktas et al., 2009). Thus, therapy based on interference of TWIST1 might be a successful strategy for chemotherapy resistant breast tumours.
Interestingly, an increase of the grade of methylation at TWIST1 promoter has been shown in breast tumours where this feature was correlated with malignant phenotypes (Fackler et al., 2003; Mehrotra et al., 2004). Despite of these findings are opposite to the oncogene behaviour of TWIST1 gene that had been addressed by other authors, no correlation has been found between TWIST1 promoter methylation and TWIST1 protein or RNA expression (Gort et al., 2008).
Entity name
High protein levels of TWIST1 have been observed in 50% of rhabdomyosarcomas. TWIST1 might play multiple roles in the formation of rhabdomyosarcomas, halting terminal differentiation, inhibiting apoptosis, and interfering with the p53 tumor-suppressor pathway (Maestro et al., 1999). Villavicencio and collaborators suggest that TWIST1 could have such oncogenic role at least in part through the activation of GLI1 which is a critical transcription factor of sonic hedgehog signalling able to prevent the exit of the cell cycle and trapping cells in proliferating myoblast pool (Villavicencio et al., 2002).
Entity name
Gastric carcinomas
TWIST1 mRNA and protein up-regulation is found with different incidences in both Lauréns classification for gastric carcinomas, with an increase of 40-60% in diffuse type and 25% in intestinal type (Rosivatz et al., 2002; Yan-Qi et al., 2007).
Furthermore, TWIST1 expression is correlated with lymph node metastasis, suggesting an association with the neoplastic transformation and subsequent development of gastric cancer (Yan-Qi et al., 2007).
In diffuse type gastric carcinomas overexpression of TWIST1 is significantly associated with the increased of expression of N-cadherin (Rosivatz et al., 2002).
This bHLH transcription factor is able to regulate the expression of several genes involved in the differentiation, adhesion, migration, invasion and proliferation of several gastric cancer cells (Feng et al., 2009). One of the most important pathways altered in this cancer cell lines is the Wnt/Tcf-4 signalling (Luo et al., 2008).
Entity name
TWIST1 is overexpressed in N-Myc-amplified neuroblastoma tumors and cell lines. This oncogenic cooperation of two key regulators of embryogenesis causes cell transformation and malignant outgrowth. While N-Myc induces cell proliferation, TWIST1 inhibits the ARF/p53 pathway involved in the Myc-dependent apoptotic response (Valsesia-Wittmann et al., 2004).
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TWIST1 expression in human gliomas is increased comparing with normal brain at mRNA and protein levels. The mRNA levels are associated with the highest grade gliomas, and increased TWIST1 expression accompanies transition from low to high grade in vivo, suggesting a role in promoting malignant progression in gliomas (Elias et al., 2005).
Entity name
Oesophageal squamous cell carcinoma
Upregulation of TWIST1 has been found in oesophageal squamous cell carcinoma (SCC), and this high level of TWIST1 was significantly associated with a greater risk for developing distant metastasis within 1 year of oesophagectomy (Yuen et al., 2007). TWIST1 has been proposed as a prognostic marker for predicting the development of distant metastasis in oesophageal SCC (Yuen et al., 2007).
The ectopic expression of TWIST1 drives to the suppression of TIMP1, a specific inhibitor of matrix metalloproteinases, promoting tumour invasion the human epithelial-like osteosarcoma cell line Saos-2 (Okamura et al., 2009).
Entity name
Pancreatic cancer
Decreased or only weak expression of TWIST1 is observed in malignant pancreatic epithelium (Hotz et al., 2007; Cates et al., 2009). However, the different expression levels of TWIST1 in pancreatic juice may be useful to differentiate pancreatic cancer from nonmalignant neoplasms, since Twist expression differed significantly between cancer and intraductal papillary mucinous neoplasm bulk tissues (Ohuchida et al., 2007). Additionally, TWIST1 could be also used as a diagnostic marker in chronic pancreatitis because decreased expression is also seen (Cates et al., 2009).
Despite of the weak expression in pancreatic cancer, it has been demonstrated that TWIST1 is activated after exposure to hypoxia in several pancreatic cancer cell lines, suggesting an important role in the invasive behavior of pancreatic tumors (Hotz et al., 2007). Several signaling molecules have been reported to be able to activate TWIST1 resulting in EMT during tumour progression in this tumour type: Axl receptor tyrosine kinase (Koorstra et al., 2009); MSX2 (Satoh et al., 2008) and VEGFR-1 (Yang et al., 2006).
Entity name
Increased TWIST1 expression and altered expression of additional transcriptional regulators implicated in embryonic development and epidermal/mesenchymal transition has been reported in melanoma cells lines and tissues. Overexpression of TWIST1 in these tumours is associated with worse outcome suggesting its use in assessing prognosis, staging, and therapy of melanoma patients (Hoek et al., 2004).
The induction of expression of TWIST1 through MFG-E8 secreted protein from tumor microenviroment has been suggested as one of the mechanisms of regulation of this bHLH transcription factor to promote progression of the disease (Jinushi et al., 2008).
Entity name
Prostate cancer
TWIST1 is highly expressed in the majority of prostate cancer tissues. Its expression levels are positively correlated with high-grade prostatic cancer and metastasis (Kwok et al., 2005; Yuen et al., 2007). Furthermore, TWIST1 is able to specifically promote metastasis to bone regulating the expression of DKK-1 via RUNX2 (Wang et al., 2006). Over-expression of TWIST results in down-regulation of p14 (ARF), which leads to the impairment of DNA damage checkpoint in response to genotoxic stress. This negative effect of TWIST on DNA damage response facilitates uncontrolled cell proliferation with genomic instability and tumorigenesis in non-malignant immortalized human prostate epithelial cell lines (Kwok et al., 2007).
TWIST1 expression has also been associated with chemotherapy and castration resistance prostate tumours through different mechanisms such as the downregulation of Y-box binding protein-1 and androgen receptor signaling respectively (Kwok et al., 2005; Shiota et al., 2009a; 2009b).
Entity name
Hepatocellular carcinoma (HCC)
TWIST1 mRNA and protein are both increased in HCC as compared to non-cancerous tissues. In addition, patients with high Twist expression have poor prognosis (Lee et al., 2006; Niu et al., 2007). These upregulated levels are associated with invasion and migration as a consequence of EMT induction and also with angiogenesis process (Niu et al., 2007; Matsuo et al., 2009).
Entity name
Epithelial ovarian carcinoma
Positive TWIST1 expression predicts a poorer overall and progression free survival in patients with epithelial ovarian carcinoma (Kajiyama et al., 2006; Hosono et al., 2007). The role of TWIST1 in tumour progression has been suggested to be associated with EMT and also with chronic paclitaxel-resistance (Kajiyama et al., 2007; Yoshida et al., 2009). There is also a significant incidence of promoter hypermethylation of TWIST1 gene promoter that could be important in early clinical diagnosis and in chemotherapeutic management and treatment of the disease (Dhillon et al., 2004).
Entity name
Endometrial cancer
TWIST1 is an independent predictor of patient survival in endometrial cancer and is correlated with E-cadherin silencing (Kyo et al., 2006). Furthermore, ionizing irradiation leads to the increased expression of TWIST1 in the HEC1A endometrial carcinoma cell line promoting cell invasion, suggesting a crucial role in the enhanced invasion after irradiation (Tsukamoto et al., 2007).
Entity name
Bladder cancer
In bladder cancer, TWIST1 overexpression is correlated with advanced-stage, high-grade tumours, metastatic lesions, negative expression of E-cadherin and positive expression of N-cadherin (Zhang et al., 2007). More importantly, TWIST1 high expression levels is associated with smoking status of the patients and with worse clinical outcome (Fondrevelle et al., 2009).
Entity name
Cervical cancer
Positive TWIST1 expression significantly predicted poorer prognosis in patients with cervical cancer (Shibata et al., 2008). Additionally, the tumour suppressor genes SFRP1 and SFRP2 decrease the invasion abilities of cervical cancer cells through the inhibition of the expression of SLUG, TWIST1 and SNAIL (Chung et al., 2009). However, the promoter methylation status of TWIST1 in combination with RAR-beta and MGMT have also been proposed as markers to distinguish between squamous cell carcinomas and negative squamous intraepithelial lesions from liquid based cytology specimens (Kim et al., 2009).
Entity name
Head and Neck cancer
TWIST1 malignant effect is dependent on different molecules like HIF-1, Fascin, EBV and AKT (Horikawa et al., 2007; Yang et al., 2008; Chen et al., 2009; Hong et al., 2009). Upregulation of TWIST1 in nasopharyngeal carcinoma cells has been associated with resistance to microtubule disrupting agents, especially taxol (Zhang et al., 2007). TWIST1 increased levels is associated with malignant parameters such as lymph node invasion and distant metastasis, and the poor prognosis of nasopharyngeal carcinoma patients (Song et al., 2006).
Entity name
Colorectal cancer
TWIST1 mRNA is upregulated in colorectal cancer patients. High levels of expression is associated with lymph node metastasis suggesting the relevance of TWIST1 in the outcome of the patients (Valdés-Mora et al., 2009). Interestingly, such increased levels are significantly associated with male gender revealing a plausible regulation through sexual hormones (Valdés-Mora et al., 2009).
Entity name
Lung cancer
Overexpression of TWIST1 is associated with poor survival of non-small cell lung cancer (NSCLC) patients (Hung et al., 2009). Again, TWIST1 is an important player in chemotherapy resistance in A549 cell raising the possibility of TWIST1 depletion as a promising approach to lung cancer therapy (Zhuo et al., 2008). Promoter hypermethylation of this gene has been also proposed as a marker of lung adenocarcinoma (Tsou et al., 2007).
Entity name
TWIST1 expression is found in malignant phechromocytomas and correlates with other EMT markers consolidating the relevant role of EMT in the malignant progression of this tumour type (Waldmann et al., 2008).


Pubmed IDLast YearTitleAuthors
195891362009Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients.Aktas B et al
165851542006N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1.Alexander NR et al
185989462008Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence.Ansieau S et al
193782512009A twist of insight - the role of Twist-family bHLH factors in development.Barnes RM et al
150307642004A twist code determines the onset of osteoblast differentiation.Bialek P et al
187661162009Epithelial-mesenchymal transition markers in pancreatic ductal adenocarcinoma.Cates JM et al
194734432009Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells.Chen SF et al
77296871995twist is required in head mesenchyme for cranial neural tube morphogenesis.Chen ZF et al
173323252007Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel.Cheng GZ et al
190952962009SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway.Chung MT et al
153281942004The contribution of genetic and epigenetic changes in granulosa cell tumors of ovarian origin.Dhillon VS et al
195499132009A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer.DiMeo TA et al
162298052005TWIST is expressed in human gliomas and promotes invasion.Elias MC et al
146010572003DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma.Fackler MJ et al
190512712009Gene expression profiling in TWIST-depleted gastric cancer cells.Feng MY et al
184408402009The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status.Fondrevelle ME et al
114860542001Patterns of gene expression during Drosophila mesoderm development.Furlong EE et al
190645462008Methylation of the TWIST1 promoter, TWIST1 mRNA levels, and immunohistochemical expression of TWIST1 in breast cancer.Gort EH et al
79584191994M-twist is an inhibitor of muscle differentiation.Hebrok M et al
152893332004Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas.Hoek K et al
192436312009Inhibition of Akt activity induces the mesenchymal-to-epithelial reverting transition with restoring E-cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells.Hong KO et al
173323242007Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma.Horikawa T et al
172114772007Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients.Hosono S et al
176998542007Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer.Hotz B et al
89881661997Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome.Howard TD et al
127025822003Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation.Howe LR et al
197789332009Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1 and Snail expression in resectable non-small cell lung cancer.Hung JJ et al
189741332008Milk fat globule EGF-8 promotes melanoma progression through coordinated Akt and twist signaling in the tumor microenvironment.Jinushi M et al
176116832007Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells.Kajiyama H et al
198360672010Assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens.Kim JH et al
192524142009The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target.Koorstra JB et al
104651221999Identification of a frameshift mutation in the gene TWIST in a family affected with Robinow-Sorauf syndrome.Kunz J et al
176901102007Role of p14ARF in TWIST-mediated senescence in prostate epithelial cells.Kwok WK et al
165649172006High Twist expression is involved in infiltrative endometrial cancer and affects patient survival.Kyo S et al
170006702006Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.Lee TK et al
20814721990Cell shape changes during gastrulation in Drosophila.Leptin M et al
75898081995Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis.Li L et al
193365152009Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells.Li QQ et al
184421942008Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells.Luo GQ et al
178987132007Tumour invasion and metastasis initiated by microRNA-10b in breast cancer.Ma L et al
104858441999Twist is a potential oncogene that inhibits apoptosis.Maestro R et al
158644832005Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer.Martin TA et al
196150902009Twist expression promotes migration and invasion in hepatocellular carcinoma.Matsuo N et al
151310502004Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung.Mehrotra J et al
153634052004Gene-regulatory interactions in neural crest evolution and development.Meulemans D et al
163222262005Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer.Mironchik Y et al
179878012007Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma.Niu RF et al
172362032007Twist, a novel oncogene, is upregulated in pancreatic cancer: clinical implication of Twist expression in pancreatic juice.Ohuchida K et al
195135662009Negative regulation of TIMP1 is mediated by transcription factor TWIST1.Okamura H et al
163068762006A twist for survival and cancer progression.Puisieux A et al
124145342002Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer.Rosivatz E et al
183491322008Up-regulation of MSX2 enhances the malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells.Satoh K et al
173432692007Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations.Seto ML et al
179252862008Twist expression in patients with cervical cancer is associated with poor disease outcome.Shibata K et al
193185822009Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth.Shiota M et al
198020012010Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression.Shiota M et al
164125612006The clinical significance of twist expression in nasopharyngeal carcinoma.Song LB et al
120864652002Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo.Soo K et al
31069321987The twist gene: isolation of a Drosophila zygotic gene necessary for the establishment of dorsoventral pattern.Thisse B et al
179671822007Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma.Tsou JA et al
179054192007Irradiation-induced epithelial-mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells.Tsukamoto H et al
190025292009TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectal cancer.Valdés-Mora F et al
156079662004Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells.Valsesia-Wittmann S et al
153417652004Tumor metastasis: a new twist on epithelial-mesenchymal transitions.Vernon AE et al
167379252006Twist overexpression promotes chromosomal instability in the breast cancer cell line MCF-7.Vesuna F et al
180629172008Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer.Vesuna F et al
119489122002Cooperative E-box regulation of human GLI1 by TWIST and USF.Villavicencio EH et al
190182642008Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival.Waldmann J et al
165962702006Identification of a unique set of genes altered during cell-cell contact in an in vitro model of prostate cancer bone metastasis.Wang J et al
147245762004Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells.Wang X et al
157364212004Expression of twist and wnt in human breast cancer.Watanabe O et al
177855502007Isolation and molecular profiling of bone marrow micrometastases identifies TWIST1 as a marker of early tumor relapse in breast cancer patients.Watson MA et al
18405171991The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes.Wolf C et al
178860952007Expression and significance of TWIST basic helix-loop-helix protein over-expression in gastric cancer.Yan-Qi Z et al
163972142006Vascular endothelial growth factor receptor-1 activation mediates epithelial to mesenchymal transition in human pancreatic carcinoma cells.Yang AD et al
152101132004Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis.Yang J et al
182970622008Direct regulation of TWIST by HIF-1alpha promotes metastasis.Yang MH et al
195366152009Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma: the important role of Snail in ovarian tumorigenesis and progression.Yoshida J et al
168228772007Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis.Yuen HF et al
173945022007Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer.Yuen HF et al
172305212007Anti-apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells.Zhang X et al
172587912007Significance of TWIST expression and its association with E-cadherin in bladder cancer.Zhang Z et al
183318242008Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway.Zhuo WL et al

Other Information

Locus ID:

NCBI: 7291
MIM: 601622
HGNC: 12428
Ensembl: ENSG00000122691


dbSNP: 7291
ClinVar: 7291
TCGA: ENSG00000122691


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807


Pubmed IDYearTitleCitations
152101132004Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis.1372
182970622008Direct regulation of TWIST by HIF-1alpha promotes metastasis.434
185989462008Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence.269
208183892010Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.227
173323252007Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel.206
213978602011Twist1-induced invadopodia formation promotes tumor metastasis.196
258939172015Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway.187
159585592005Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target.165
222532302012Epithelial-mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1.160
104858441999Twist is a potential oncogene that inhibits apoptosis.143


Fátima Valdés-Mora ; Teresa Gómez del Pulgar ; Juan Carlos Lacal

TWIST1 (twist homolog 1 (Drosophila))

Atlas Genet Cytogenet Oncol Haematol. 2009-11-01

Online version: