TWIST2 (twist family BHLH transcription factor 2)

2014-06-01   Daniela Gasparotto , Erica Lorenzetto 

Experimental Oncology 1, (CRO) National Cancer Institute, Aviano 33081, Italy


Atlas Image



This gene is localized at chromosome 2q37.3 (Perrin-Schmitt et al., 1997) and has 2 exons (Šošic et al., 2003).


TWIST2 DNA sequence contains 2 exons separated by a large intron, with the entire coding region located in exon 1 (Šošic et al., 2003). Two transcript variants encoding the same protein have been described: variant 1 of 1434 bp and variant 2 of 1186 bp. Both variants encode a same protein but have different 3 UTR ( NCBI).


No pseudogene of TWIST2 is known.


Atlas Image
Structure of TWIST2 protein. The protein domains and their length (indicated by number of limiting residues) are reported. TWIST2 contains 2 nuclear localization signals, a basic helix loop helix (bHLH) domain and a TWIST box domain (Modified from Gong and Li, 2002).


The TWIST2 gene encodes a 160 aminoacid protein with a predicted molecular weight of 19 kDa (Li et al., 1995; Lee et al., 2000; Gong and Li, 2002).
TWIST2 structure includes 2 nuclear localization signals at the N-terminus (aa 31-34, aa 49-53), a basic helix-loop-helix (bHLH) domain (aa 66-117) and a C-terminal TWIST box region (aa 141-160) (Gong and Li, 2002).
Post transcriptional phosphorylation at Ser55 is predicted for both human and rodent protein ( phosphosite). The bHLH domain includes highly conserved Thr and Ser residues whose posphorylation has been demonstrated to affect dimer formation and DNA binding affinity in other TWIST family members (Firulli et al., 2005; Firulli and Conway, 2008).


TWIST2 is involved in mesodermal patterning and in differentiation of multiple cell lineages including muscle, cartilage, osteogenic, adipogenic and myeloid cells (Lee et al., 2000; Gong and Li, 2002; Lee et al., 2003; Sharabi et al., 2008). In human embryonic tissues TWIST2 protein is detectable in early chondroblast cells in cartilage plate and surrounding mesenchymal cells, especially near the tip of the digits (Lee et al., 2000). In the skin, it is expressed early in the undifferentiated mesenchymal layer beneath the epidermis that will develop into dermis (Lee et al., 2000). TWIST2 is expressed in myeloid progenitors (Sharabi et al., 2008). In adult tissues, TWIST2 is expressed in the bone marrow (Ishikawa et al., 2013). A low level of expression has been reported in glands and tubules (Lee et al., 2000) as well as liver, muscle, pancreas, and adipose tissue (Pettersson et al., 2010). It should be pointed out that many antibodies used to detect the expression of TWIST proteins recognize both members of the family, making it hard to actually assess the specific contribution of each protein.


Nuclear in embryonic tissues, predominantly cytoplasmic in adult tissues (Lee et al., 2000).


TWIST2 is a transcription factor belonging to the bHLH (basic helix loop helix) family (Li et al., 1995; Lee et al., 2000). bHLH proteins form homo- or heterodimers with other bHLH family members and, as dimers, bind DNA through the bHLH domain at cis regulatory motifs, termed E-box (CANNTG), leading to either activation or inhibition of transcription (Murre et al., 1989; Franco et al., 2011b). The specificity of the dimers depends on several factors: partner choice, phosphorylation, other protein-protein interactions and spatial-temporal expression (Murre et al., 1989; Franco et al., 2011b). The partner choice depends mainly on the availability and on the phosphorylation status of the partner (Firulli and Conway, 2008).
TWIST2, similar to TWIST1, may also control gene expression by epigenetic modulation of the promoter: TWIST1-2 interacts with and recruits histone acetyl transferases/histone deacetylases to the promoter regulatory region, resulting in transcriptional repression through histone modification (Hamamori et al., 1999; Gong and Li, 2002; Lee et al., 2003).
Role in embryonic development
Murine Twist2 was identified through yeast-two-hybrid screen (Staudinger et al., 1993) and it was named Dermo1 for its expression pattern in the dermis of mouse embryo (Li et al., 1995). Dermo1 was later renamed Twist2 (Šošic et al., 2003) based on its high homology and overlapping expression pattern with Twist1 (Li et al., 1995; Lee et al., 2000; ŠoŠic et al., 2003). During mouse embryogenesis Twist2 displays a spatial expression pattern similar to Twist1, but temporally delayed (Li et al., 1995; Lee et al., 2000). Twist2 is expressed at a lower level in the sclerotome and dermatome of the somites, and in the limb buds at Day 10.5, and accumulates predominantly in the dermatome, prevertebrae, and the derivatives of the branchial arches by Day 13.5 (Li et al., 1995). As differentiation of prechondrial cells proceeds, Twist2 becomes restricted to the perichondrium (Li et al., 1995). In the dermis, expression increases continuously through Day 17.5, is detectable in newborns but is then downregulated in adult tissues (Li et al., 1995). An analogous role has been reported for Twist2 in avian limb outgrowth and patterning (Wade et al., 2012) as well as skin development (Scaal et al., 2001).
TWIST2 plays an important role in early bone development, acting as a negative regulator of osteoblast differentiation. Indeed, TWIST2 represses osteoblast maturation maintaining cells in a preosteoblast phenotype (Tamura and Noda, 1999; Lee et al., 2000) and it inhibits bone specific gene expression (Zhang et al., 2008). TWIST2 is involved in the modulation of the activity of Runx2, a master regulator of osteogenic program, both at the transcriptional level and at the protein level (Bialek et al., 2004; Zhang et al., 2008). By interacting with Runx2, TWIST2 inhibits the expression of Runx2 downstream targets, thus blocking the osteogenesis program (Lee et al., 2003). Runx2 can be downregulated by ERK, therefore ERK cooperates with TWIST2 in the inhibition of osteoblast differentiation (Nakamura et al., 2010). Insulin receptor signaling also controls osteoblast development by suppressing TWIST2 (Fulzele et al., 2010; Ulrich et al., 2013). In osteoblast TWIST2 physically interacts with ATF4 affecting its DNA binding function (Danciu et al., 2012). During cranial cell development TWIST2 is a mediator of Wnt signaling in specifying dermal cell fate and suppressing the cartilage cell fate (Tran et al., 2010).
TWIST2 is furthermore involved in the inhibition of muscle differentiation program acting as a transcriptional repressor of MyoD, the activation of which typically requires the binding of MEF2 (Gong and Li, 2002). TWIST2 needs histone deacetylases (HDAC) to exert Myo-MEF2 inhibition (Gong and Li, 2002). TWIST2 is also a critical regulator of adipose tissue homeostasis acting as a physical inhibitor of the transcription factor ADD1/SREBP1c, involved in adipocyte differentiation (Lee et al., 2003).
TWIST2 is required for normal corneal keratocyte proliferation and eyelid morphogenesis. Loss of TWIST2 leads to corneal thinning, due to early cessation of proliferation of corneal stromal progenitors, resulting in fewer mature stromal keratocytes for the production of the corneal matrix (Weaving et al., 2010).
In myeloid lineage development, TWIST2 inhibits the proliferation and the differentiation of granulocyte macrophage progenitors (Sharabi et al., 2008). TWIST2-null 129/Sv mice undergo almost normal embryonic development but die within the first two weeks after birth due to cachexia and high levels of proinflammatory cytokines (Šošic et al., 2003). However, the phenotype is influenced by genetic background. In fact TWIST2-null mice in the 129/C57 mixed background survive with only a mild disease and facial signs reminiscent of facial dermal dysplasia (Setleis syndrome), the human disease associated with germline TWIST2 inactivating mutations (Tukel et al., 2010).
Role in hematopoiesis and inflammation
TWIST2 is constitutionally expressed in myeloid progenitors where negatively controls myeloid lineage differentiation into macrophages, neutrophils and basophils (Sharabi et al., 2008). TWIST2 regulates the function of mature myeloid cells by promoting the expression of the anti-inflammatory cytokine interleukin-10 and inhibiting the production of pro-inflammatory cytokines interleukin-12 and interferon-γ (Sharabi et al., 2008). TWIST2 expression is also induced by NF-kB, as part of a negative feedback loop in which cytokines activate NF-kB and downstream activation of TWIST2 results in repression of NF-kB activation (Šošic et al., 2003).
In T lymphocytes and in immature thymocytes TWIST2 inhibits galectin-1-induced apoptosis, a process implicated in thymic negative selection (Koh et al., 2008; Koh et al., 2009; Merindol et al., 2014). TWIST2 prevents NF-kB mediated expression of galectin receptor (CD7), therefore inhibiting galectin1/CD7-mediated apoptosis (Koh et al., 2008; Koh et al., 2009; Merindol et al., 2014).
Role in apoptosis and senescence
TWIST2 antagonizes oncogene-induced cell failsafe programs, apoptosis and senescence. In a genetic screen for antiapoptotic proteins, TWIST2 was demonstrated to protect cells from Myc and E1A-induced apoptosis by modulating the ARF/MDM2/p53 pathway (Maestro et al., 1999).
TWIST2 overcomes oncogene-induced premature senescence by abrogating the transcription of p16Ink4A and p21Cip1, key regulators of the p53- and RB-dependent pathways (Ansieau et al., 2008).
Role in oxidative stress
TWIST2 participates in the control of reactive oxygen species (ROS) and in cellular response to oxidative stress. TWIST2 lowers the level of intracellular ROS and displays an antioxidant activity in several cell types. TWIST-driven inhibition of oxidative stress is involved in the protection of cells against c-Myc induced apoptosis (Floch et al., 2013).
Role in stemness (cancer stem cells)
TWIST2 mediates mesenchymal stem cell (MSC) self-renewal by maintaining the immature phenotype of human MSC and inhibiting osteogenesis and chondrogenesis (Isenmann et al., 2009). In mouse, the inhibition of MSC differentiation induced by fibroblast growth factor 2 (Fgf2) is strongly correlated with the upregulation of TWIST2 and Spry4 and with the suppression of Erk1/2 activation (Lai et al., 2011). TWIST2-expressing cells exhibit an increased expression of stem cell markers Bmi-1, Sox2, CD24, Nanog and an increased capacity of self-renewal (Liu et al., 2014).
Role in EMT
TWIST2 has been involved in epithelial-mesenchymal transition (EMT), a process by which cells lose epithelial characteristics and acquire a migratory, mesenchymal phenotype. EMT is associated with downregulation of epithelial markers, such as E-cadherin, and induction of mesenchymal markers, such as N-cadherin. EMT has an essential role in embryonic development and in the initial steps of tumor invasion and metastasis. Several bHLH transcription factors are involved in the regulation of EMT. TWIST2 has been implicated in EMT in several experimental models and cancer types (Tsuji et al., 2008; Katoh and Katoh, 2009; Ponnusamy et al., 2010; Fang et al., 2011; Akkari et al., 2012; Amatangelo et al., 2012; Salnikov et al., 2012; Shimoda et al., 2012; Mao et al., 2012; Mao et al., 2013; Teng and Li, 2014; Díaz-Martín et al., 2014). A dynamic interaction between EMT and stemness gene programs has been observed in prostate and bladder cancer cell experimental models (Celià-Terrassa et al., 2012).
Atlas Image


TWIST genes are evolutionary conserved from jellyfish to human. Duplications and deletions of TWIST genes occurred during vertebrate evolution (Germanguz et al., 2007; Gitelman, 2007).
The human TWIST2 protein shares 98.8% amino acid identity to mouse and rat and 95% to chicken Twist2 (Lee et al., 2000).
Within the bHLH protein family, TWIST2 displays the highest level of sequence similarity with TWIST1. The two proteins are near identical in the C-terminal Helix-Loop-Helix (HLH) and TWIST BOX domains, while they display some divergence in the N-terminal region (Lee et al., 2000; Gong and Li, 2002; Barnes and Firulli, 2009).



TWIST2 nonsense mutations have been associated with Focal Facial Dermal Dyspasia type III (Setleis syndrome), a developmental defect characterized by bitemporal or pre auricolar facial dermal dysplasia (Tukel et al., 2010; Cervantes-Barragán et al., 2011; Franco et al., 2011a; Girisha et al., 2014).


Missense mutations have been found in endometrial cancer COSMIC

Implicated in

Entity name
Breast cancer
TWIST2 overexpression has been implicated in breast cancer. TWIST2 protein was reported to be expressed in 94% of breast cancers and in 100% of nodal metastases. In mammary cell lines TWIST2 ectopic overexpression induced EMT, enhanced cell migration, colony formation, and tumor growth in vivo. TWIST2 induced the expression of stem cell markers thereby increasing the abundance of a CD44high/CD24low subpopulation with stem-like self renewal capacities (Fang et al., 2011).
Mao et al. (2012) observed TWIST2 expression, most frequently in ductal and in squamous cell breast carcinomas. Expression pattern was cytoplasmic in cells localized in tumor centre and in lymph node metastases, while TWIST2 displayed nuclear expression and associated with EMT features (fibroblast-like morphology, E-cadherin loss) in cells at the invasive front. TWIST2 cytoplasmic positive expression was associated with advanced TNM, advanced clinical stage and metastasis (Mao et al., 2012).
Entity name
Cervical cancer
Li et al. (2012) investigated TWIST2 and E-cadherin protein expression in different stages and grades of cervical dysplasia and squamous cell carcinoma (SCC). All SCCs were positive for cytoplasmic TWIST2 expression, and in 87.1% specimens staining were also nuclear. In contrast, only 7.1% of healthy cervical samples showed weak/moderate cytoplasmic or nuclear positivity. TWIST2 positivity was associated with aberrant E-Cadherin cytoplasmic localization. TWIST2 cytoplasmic expression was associated with significantly increased risk of metastasis (Li et al., 2012).
Entity name
Colorectal cancer
TWIST2 expression was demonstrated by immunohistochemistry in 71% of colorectal cancers. The pattern of staining was mainly cytoplasmic and was associated with reduced E-cadherin. Positive TWIST2 expression was associated with poor disease-free and overall survival (Yu et al., 2013).
Long et al. (2013) observed decreased expression of mir-138 in colorectal cancers compared to healthy tissues and provided evidence that mir-138 targeted TWIST2. Indeed, overexpression of TWIST2 was inversely correlated with mir-138 and associated with metastasis and poor prognosis (Long et al., 2013).
Entity name
Ovarian cancer
Mao et al. (2013) reported overexpression of TWIST2 in 16/22 ovarian tumors compared to healthy tissue. The high level of TWIST2 was positively correlated with HIF-1α. In the HO-8910 ovarian cell line, TWIST2 overexpression protected cells from apoptosis under hypoxic condition through activation of the PI3K/AKT survival pathway. In a following study, the same authors confirmed TWIST2 overexpression in 59/84 (70%) ovarian cancers. The pattern of expression was both nuclear and cytoplasmatic, and the fraction of TWIST2-positive cases was increased along with the FIGO stage. In the ovarian cell line SKOV-3 the ectopic expression of TWIST2 induced EMT, β-catenin nuclear accumulation and activation of the Wnt pathway (Mao et al., 2013).
Entity name
Head and Neck squamous cell carcinomas (HNSCC)
TWIST2 gene expression was increased in 87% esophageal squamous cell carcinomas (Ansieau et al. 2008). In tongue squamous cell carcinomas overexpression of TWIST2 was detected in 45% of tumors and was associated with hypoxia. The concomitant expression of more than two of the markers TWIST2, HIF-1α, and SNIP1 was associated with poor survival (Liang et al., 2011).
In salivary adenoid cystic carcinoma the coexpression of TWIST2, HIF-2α and SIP1 was associated with perineural invasion, local recurrence, distant metastasis and shorter survival (Zhou et al., 2012).
In HNSCCs TWIST2 overexpression was correlated with high tumor grade and short survival in oral cavity/pharynx cancer patients. In these tumors, TWIST2 expression was not associated with EMT markers. Instead, within the N-positive group, identified subset of tumors with high risk of progression (Gasparotto et al., 2011).
Entity name
In leukemias TWIST2 has oncosuppressive role. Raval et al. (2005) reported epigenetic silencing of TWIST2 in chronic lymphocytic leukemia (CLL), and provided evidence that expression of this transcription factor was related to the degree of promoter methylation. In this study, TWIST2 promoter methylation was more frequent in the IgVH-mutated CLL subset (Raval et al., 2005). In acute lymphoblastic leukemia (ALL) the TWIST2 promoter was hypermethylated in 50% of cases. In ALL cell lines the restoration of TWIST2 expression reduced cell growth, induced apoptosis and increased sensitivity to chemotherapeutic agents (Thathia et al., 2012).
Entity name
Hepatocellular carcinomas (HCC)
TWIST2 was found to be overexpressed in human HCCs. Ectopic expression of TWIST2 in HCC cell lines induced EMT, augmented cell migration, invasion and colony-forming abilities in vitro and promoted tumor growth in vivo. Moreover, TWIST2 promoted cancer stem-like cell self-renewal via upregulation of CD24 expression (Liu et al., 2014).
TWIST2 was also implicated in the process of oncogenic transformation of primary hepatocytes by Hepatitis C virus (HCV). The viral protein NS5A either alone or in the context of other viral components in the course of infection, acted through TWIST2 activation to disrupt cell polarity, and, in cooperation with Ras, induced cell transformation and metastastatic spread in vivo (Akkari et al., 2012).
Entity name
By investigating the role of TWIST in soft tissue sarcomas, Piccinin et al. (2012) demonstrated overexpression of TWIST1 and TWIST2 proteins in 60% and in 7% of tumors, respectively. TWIST1/2 contributed to transformation of primary mesenchymal cells in vitro and to tumor growth in mice by antagonizing p53. By directly interacting with p53, TWIST1/2 hindered p53 phosphorylation at Ser 392, thereby facilitating MDM2-mediated p53 degradation (Piccinin et al., 2012).
In osteosarcoma TWIST2 demonstrated a tumor suppressive role (Ishikawa et al., 2013). In human osteosarcomas TWIST2 mRNA level was downregulated compared with bone marrow stem cells. In a murine model, TWIST2 correlated inversely with tumorigenic potential. The tumor suppressor activity of TWIST2 was correlated with the inhibition of the formation of a microenvironment favourable for tumor growth (Ishikawa et al., 2013).
Entity name
TWIST2 expression was significantly increased in melanomas (60%) compared to their normal counterparts, as well as in melanoma cell lines (Ansieau et al., 2008).
TWIST1/2 inhibited premature senescence by abrogating p16 INK4A and p21 cip activation and promoted EMT in cooperation with mitogenic signaling activation (Ansieau et al., 2008).
Entity name
Focal facial dermal dysplasia type III, or Setleis syndrome
Focal facial dermal dysplasia type III, or Setleis syndrome (OMIM entry 607556). The disease was first described in consanguineous patients in Puerto Rican families (Setleis et al., 1963). Patients exhibit bilateral temporal preauricular marks and other facial abnormalities, including absent eyelashes on both lids or multiple rows on the upper lids, slanted eyebrows chin clefting, and other nonfacial manifestations (Tukel et al., 2010, Cervantes-Barragán et al., 2011). The disease is panethnic (Tukel et al., 2010). The mode of inheritance of Setleis syndrome has been reported as autosomal recessive or autosomal dominant with decreased manifestations in heterozygotes (Tukel et al., 2010, Cervantes-Barragán et al., 2011).
Entity name
2q37 deletion syndrome
TWIST2 has been proposed as candidate gene of the 2q37 deletion syndrome due to its localization in the smallest deleted chromosome region (Leroy et al., 2013).
Patients exhibit facial dysmorphism and brachydactyly, behavioural problems, autism of varying severity and overweight or obesity (Leroy et al., 2013).


Pubmed IDLast YearTitleAuthors
227504662012Hepatitis C viral protein NS5A induces EMT and participates in oncogenic transformation of primary hepatocyte precursors.Akkari L et al
227918122012c-Myc expression and MEK1-induced Erk2 nuclear localization are required for TGF-beta induced epithelial-mesenchymal transition and invasion in prostate cancer.Amatangelo MD 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
219311732011Setleis syndrome in Mexican-Nahua sibs due to a homozygous TWIST2 frameshift mutation and partial expression in heterozygotes: review of the focal facial dermal dysplasias and subtype reclassification.Cervantes-Barragán DE et al
218665692012The basic helix loop helix transcription factor Twist1 is a novel regulator of ATF4 in osteoblasts.Danciu TE et al
241222922014A core microRNA signature associated with inducers of the epithelial-to-mesenchymal transition.Díaz-Martín J et al
216028792011Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal.Fang X et al
188556842008Phosphoregulation of Twist1 provides a mechanism of cell fate control.Firulli AB et al
157356462005Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities.Firulli BA et al
239673082013Modulation of oxidative stress by twist oncoproteins.Floc'h N et al
209350572011Redundant or separate entities?--roles of Twist1 and Twist2 as molecular switches during gene transcription.Franco HL et al
207143422011The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis.Fu J et al
206554712010Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition.Fulzele K et al
222016132011Overexpression of TWIST2 correlates with poor prognosis in head and neck squamous cell carcinomas.Gasparotto D et al
176854772007Four twist genes in zebrafish, four expression patterns.Germanguz I et al
241270072014A novel frameshift mutation in TWIST2 gene causing Setleis syndrome.Girisha KM et al
175675942007Evolution of the vertebrate twist family and synfunctionalization: a mechanism for differential gene loss through merging of expression domains.Gitelman I et al
118097512002Dermo-1, a multifunctional basic helix-loop-helix protein, represses MyoD transactivation via the HLH domain, MEF2 interaction, and chromatin deacetylation.Gong XQ et al
100254061999Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A.Hamamori Y et al
196099392009TWIST family of basic helix-loop-helix transcription factors mediate human mesenchymal stem cell growth and commitment.Isenmann S et al
235571742013Twist2 functions as a tumor suppressor in murine osteosarcoma cells.Ishikawa T et al
194245922009Integrative genomic analyses of ZEB2: Transcriptional regulation of ZEB2 based on SMADs, ETS1, HIF1alpha, POU/OCT, and NF-kappaB.Katoh M et al
199371402009Twist2 regulates CD7 expression and galectin-1-induced apoptosis in mature T-cells.Koh HS et al
216080802011Fibroblast growth factor 2 (Fgf2) inhibits differentiation of mesenchymal stem cells by inducing Twist2 and Spry4, blocking extracellular regulated kinase activation, and altering Fgf receptor expression levels.Lai WT et al
110623442000Human Dermo-1 has attributes similar to twist in early bone development.Lee MS et al
146546922003Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c.Lee YS et al
230733102013The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients.Leroy C et al
75898081995Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis.Li L et al
220188732012Correlation of TWIST2 up-regulation and epithelial-mesenchymal transition during tumorigenesis and progression of cervical carcinoma.Li Y et al
211677682011Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma.Liang X et al
241935122014Twist2 promotes self-renewal of liver cancer stem-like cells by regulating CD24.Liu AY et al
241719262013Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2.Long L et al
104858441999Twist is a potential oncogene that inhibits apoptosis.Maestro R et al
242442942013The role of nuclear β-catenin accumulation in the Twist2-induced ovarian cancer EMT.Mao Y et al
231335632012Significance of heterogeneous Twist2 expression in human breast cancers.Mao Y et al
247696472014The emerging role of Twist proteins in hematopoietic cells and hematological malignancies.Merindol N et al
25032521989Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.Murre C et al
204484052010Potential involvement of Twist2 and Erk in the regulation of osteoblastogenesis by HB-EGF-EGFR signaling.Nakamura T et al
90610341997The locations of the H-twist and H-dermo-1 genes are distinct on the human genome.Perrin-Schmitt F et al
200079352010A possible inflammatory role of twist1 in human white adipocytes.Pettersson AT et al
229753812012A "twist box" code of p53 inactivation: twist box: p53 interaction promotes p53 degradation.Piccinin S et al
206973462010MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells.Ponnusamy MP et al
158094522005TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia.Raval A et al
230500242012Hypoxia induces EMT in low and highly aggressive pancreatic tumor cells but only cells with cancer stem cell characteristics acquire pronounced migratory potential.Salnikov AV et al
111950852001cDermo-1 expression indicates a role in avian skin development.Scaal M et al
190906212008Twist-2 controls myeloid lineage development and function.Sharabi AB et al
229311652012The T-box transcription factor Brachyury regulates epithelial-mesenchymal transition in association with cancer stem-like cells in adenoid cystic carcinoma cells.Shimoda M et al
125539062003Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity.Šošić D et al
83831201993Interactions among vertebrate helix-loop-helix proteins in yeast using the two-hybrid system.Staudinger J et al
100224991999Identification of DERMO-1 as a member of helix-loop-helix type transcription factors expressed in osteoblastic cells.Tamura M et al
241583542014The roles of HLH transcription factors in epithelial mesenchymal transition and multiple molecular mechanisms.Teng Y et al
220582082012Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity.Thathia SH et al
209804042010Role of canonical Wnt signaling/ß-catenin via Dermo1 in cranial dermal cell development.Tran TH et al
190749072008Epithelial-mesenchymal transition induced by growth suppressor p12CDK2-AP1 promotes tumor cell local invasion but suppresses distant colony growth.Tsuji T et al
206914032010Homozygous nonsense mutations in TWIST2 cause Setleis syndrome.Tukel T et al
237635162013Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors Runx2 and Twist2.Ulrich C et al
228844972012Twist2 contributes to termination of limb bud outgrowth and patterning through direct regulation of Grem1.Wade C et al
205740242010Twist2: role in corneal stromal keratocyte proliferation and corneal thickness.Weaving L et al
236136362013Twist2 is a valuable prognostic biomarker for colorectal cancer.Yu H et al
186551822008Intricate gene regulatory networks of helix-loop-helix (HLH) proteins support regulation of bone-tissue related genes during osteoblast differentiation.Zhang Y et al
221039742012Coexpression of hypoxia-inducible factor-2α, TWIST2, and SIP1 may correlate with invasion and metastasis of salivary adenoid cystic carcinoma.Zhou C et al

Other Information

Locus ID:

NCBI: 117581
MIM: 607556
HGNC: 20670
Ensembl: ENSG00000233608


dbSNP: 117581
ClinVar: 117581
TCGA: ENSG00000233608


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205


Pubmed IDYearTitleCitations
185989462008Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence.269
216028792011Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal.80
258950232015Metastasis-associated in colon cancer-1 promotes vasculogenic mimicry in gastric cancer by upregulating TWIST1/2.36
158094522005TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia.34
241935122014Twist2 promotes self-renewal of liver cancer stem-like cells by regulating CD24.30
211677682011Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma.26
220188732012Correlation of TWIST2 up-regulation and epithelial-mesenchymal transition during tumorigenesis and progression of cervical carcinoma.26
174875582007Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma.25
241719262013Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2.24
242442942013The role of nuclear β-catenin accumulation in the Twist2-induced ovarian cancer EMT.24


Daniela Gasparotto ; Erica Lorenzetto

TWIST2 (twist family BHLH transcription factor 2)

Atlas Genet Cytogenet Oncol Haematol. 2014-06-01

Online version: