title: Significance of heterogeneous Twist2 expression in human breast cancers.
abstract: BACKGROUND
  Twist2 (Dermo1) has been shown to mediate the epithelial-mesenchymal transition (EMT) to promote tumor invasion and even metastasis. However, the involvement of EMT in breast cancer progression is highly debated, partially due to clinical observations showing that the majority of human breast carcinoma metastases express E-cadherin and maintain their epithelial morphology. The molecular mechanism by which Twist2 participates in EMT of breast cancer in vivo remains poorly understood.
  
  
  METHODS
  We examined Twist2 expression pattern in human breast carcinomas by western blot and tissue microarray, and analyzed Twist2 cellular localization by confocal microscopy, cell fractionation and other approaches.
  
  
  RESULTS
  Twist2 expression was significantly increased in breast cancer. Cytoplasmic Twist2 positive cancer cells expressing E-cadherin on the cellular membrane were mainly located at tumor center of primary carcinomas and lymph metastases, while cancer cells with nuclear Twist2 clearly showed loss of E-cadherin and were detected at the invasive front in ductal breast carcinomas. In addition, ectopically stable-expressed Twist2 was found to localize in the cytoplasm of cancer cells. Collectively, these data indicate that upregulation of cytoplasmic Twist2 is correlated with tumor histological type and tumor metastasis in human breast cancers.
  
  
  CONCLUSIONS
  The differential cellular distribution of Twist2 may be associated with tumor progression. The cytoplasmic Twist2 in cancer cells at tumor center of primary carcinomas and lymph metastases contributes to the maintenance of epithelial cancer characteristics expressing E-cadherin in a noninvasive state, while the nuclear Twist2 at the cancer invasion front activates EMT to deprive epithelial property of neoplastic cells, thus facilitating invasion and metastasis. These findings suggest that heterogeneous expression of Twist2 in tumors may have a functional link to tumor progression.
authors.affiliation: Department of Pathophysiology in Basic Science, Medical College of Xiamen University, Xiamen, Fujian, China. maoyubin@xmu.edu.cn
authors.forename: Yubin
authors.initials: Y
authors.lastname: Mao
authors.forename: Nini
authors.initials: N
authors.lastname: Zhang
authors.forename: Jinfei
authors.initials: J
authors.lastname: Xu
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Ding
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zong
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D009362:Neoplasm Metastasis; D012097:Repressor Proteins / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; C486274:TWIST2 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1