MSX2 (Msh Homeobox 2)

2013-11-01   Kennichi Satoh 

Division of Cancer stem cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Shiote, Medeshima, Natori city, Miyagi 981-1293, Japan





MSX2 contains two exons. The length of MSX2 gene is 6328 bases.


2224 bases mRNA; 801 bases of coding region.


One pseudogene was reported (Hodgkinson et al., 1993).



This gene encodes a member of the muscle segment homeobox gene family that consists of 267 amino acids. The molecular weight of the encoded protein is about 29 kDa. MSX2 is a transcriptional repressor which regulates a balance between survival and apoptosis of neural crest-derived cells for proper craniofacial morphogenesis (Davidson, 1995). MSX2 is also shown to be an important target for the RAS signaling pathways (Takahashi et al., 1996). The expression pattern of this gene in the development of organs suggests its pivotal role in epithelial-mesenchymal interactions (Satoh et al., 2004). On the other hand, accumulating evidence has revealed the active involvement of this gene in tumorigenesis and/or tumor development (Satoh et al., 2012).


The expression of MSX2 is observed in a variety of sites, including premigratory cranial neural crest, tooth, and mammary gland, etc (Takahashi and Le Douarin, 1990; Davidson, 1995; Satoh et al., 2004). In addition, enhanced expression of MSX2 is found in several cancer species (Satoh et al., 2012).


Located at cell nuclei.


MSX2 act as a transcriptional regulator in the development multiple organs such as bone, neural crest and mammary gland, and play a role in limb-pattern and teeth formation (Davidson, 1995). MSX2 may induce the proliferation of osteoprogenitors (Dodig et al., 1999), as well as osteoblasts (Liu et al., 1999), and this gene was also related to the enhancement of branching morphogenesis in mouse mammary ducts (Satoh et al., 2007).


Mus musculus Msx2; Xenopus laevis msx2-A; Drosophila melanogaster Dr.



Mutations in this gene are associated with Boston type craniosynostosis (Jabs et al., 1993).

Implicated in

Entity name
Pancreatic cancer
MSX2 is shown to be indispensable for BMP-induced epithelial to mesenchymal transition (EMT) in pancreatic cancer cells (Hamada et al., 2007) . Increased expression of this gene was significantly correlated with higher tumor grade, vascular invasion and Twist 1 expression (Satoh, et al., 2008). In addition, MSX2 has been shown to enhance the chemoresistance through ABCG2 induction and increase in the cancer stem cell phenotype (Hamada et al., 2012; Satoh et al., 2012) (Figure 1).
Atlas Image
Entity name
Gastric cancer
MSX2 was identified as a cancer- specific hedgehog target and the down-regulation of this gene resulted in the inhibition of cancer cell growth in vitro (Ohta et al., 2009).
Entity name
Ovarian cancer
MSX2 has been shown to be a downstream target of WNT signal and has been correlated with the invasiveness of ovarian endometrioid adenocarcinoma (Zhai et al., 2011).
Entity name
Breast carcinoma
The expression of this gene was associated with good prognosis in breast cancer patients (Lanigan et al., 2010).
Entity name
Malignant melanoma
The expression of this gene was associated with good prognosis in malignant melanoma patients (Gremel et al., 2011).
Entity name
Prostate carcinoma
This gene expression was increased significantly in tumors with metastasis compared to those without metastasis in prostate carcinoma (Chua et al., 2010).


Pubmed IDLast YearTitleAuthors
210917722010Differential expression of MSX2 in nodular hyperplasia, high-grade prostatic intraepithelial neoplasia and prostate adenocarcinoma.Chua CW et al
74827671995The function and evolution of Msx genes: pointers and paradoxes.Davidson D et al
103289221999Ectopic Msx2 overexpression inhibits and Msx2 antisense stimulates calvarial osteoblast differentiation.Dodig M et al
217309742011Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma.Gremel G et al
214654792012The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2.Hamada S et al
81014531993Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells.Hodgkinson JE et al
81061711993A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis.Jabs EW et al
206820662010Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro.Lanigan F et al
99173621999Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans.Liu YH et al
191071312009Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers.Ohta H et al
153000132004Msx-1 and Msx-2 in mammary gland development.Satoh K et al
231624732012MSX2 in pancreatic tumor development and its clinical application for the diagnosis of pancreatic ductal adenocarcinoma.Satoh K et al
175460502007Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2.Satoh K et al
86683391996Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene.Takahashi C et al
19771611990cDNA cloning of a quail homeobox gene and its expression in neural crest-derived mesenchyme and lateral plate mesoderm.Takahashi Y et al
214993002011MSX2 is an oncogenic downstream target of activated WNT signaling in ovarian endometrioid adenocarcinoma.Zhai Y et al

Other Information

Locus ID:

NCBI: 4488
MIM: 123101
HGNC: 7392
Ensembl: ENSG00000120149


dbSNP: 4488
ClinVar: 4488
TCGA: ENSG00000120149


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
165405162006Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis.74
163278842005Medical sequencing of candidate genes for nonsyndromic cleft lip and palate.70
127502902003Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells.62
180560362007Vascular Bmp Msx2 Wnt signaling and oxidative stress in arterial calcification.52
176930622007Concerted action of Msx1 and Msx2 in regulating cranial neural crest cell differentiation during frontal bone development.46
215122812011Activation of receptor for advanced glycation end products induces osteogenic differentiation of vascular smooth muscle cells.31
205389602010A candidate gene study of obstructive sleep apnea in European Americans and African Americans.30
183491322008Up-regulation of MSX2 enhances the malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells.27
200046462010Tumor necrosis factor-alpha increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction.27


Kennichi Satoh

MSX2 (Msh Homeobox 2)

Atlas Genet Cytogenet Oncol Haematol. 2013-11-01

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