title: Over-Expressed Twist Associates with Markers of Epithelial Mesenchymal Transition and Predicts Poor Prognosis in Breast Cancers via ERK and Akt Activation.
abstract: Overexpression of Twist, a highly conserved basic helix-loop-helix transcription factor, is associated with epithelial-mesenchymal transition (EMT) and predicts poor prognosis in various kinds of cancers, including breast cancer. In order to further clarify Twist's role in breast cancer, we detected Twist expression in breast cancer tissues by immunohistochemistry. Twist expression was observed in 54% (220/408) of breast cancer patients and was positively associated with tumor size, Ki67, VEGF-C and HER2 expression. Conversely, Twist was negatively associated with estrogen receptor (ER), progesterone receptor (PgR) and E-cadherin expression. Patients with Twist expression had a poorer prognosis for 30-month disease free survival (DFS) (82.9%) than patients with negative Twist (92.3%). Overexpression of Twist led to dramatic changes in cellular morphology, proliferation, migratory/invasive capability, and expression of EMT-related biomarkers in breast cancer cells. Moreover, we show that Twist serves as a driver of tumorigenesis, as well as an inducer of EMT, at least in part, through activation of the Akt and extracellular signal-regulated protein kinase (ERK) pathways which are critical for Twist-mediated EMT. Our results demonstrate that Twist expression is an important prognostic factor in breast cancer patients.
authors: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China; Cancer Research Center of Shantou University Medical College, Shantou, Guangdong, China.
authors: Yong-Qu
authors: YQ
authors: Zhang
authors: Department of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Xiao-Long
authors: XL
authors: Wei
authors: Cancer Research Center of Shantou University Medical College, Shantou, Guangdong, China; Changjiang Scholar's Research Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Yuan-Ke
authors: YK
authors: Liang
authors: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China; Changjiang Scholar's Research Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Wei-Ling
authors: WL
authors: Chen
authors: Changjiang Scholar's Research Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Fan
authors: F
authors: Zhang
authors: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China; Cancer Research Center of Shantou University Medical College, Shantou, Guangdong, China; Changjiang Scholar's Research Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Jing-Wen
authors: JW
authors: Bai
authors: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Si-Qi
authors: SQ
authors: Qiu
authors: Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Cai-Wen
authors: CW
authors: Du
authors: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Wen-He
authors: WH
authors: Huang
authors: The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China; Cancer Research Center of Shantou University Medical College, Shantou, Guangdong, China; Changjiang Scholar's Research Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors: Guo-Jun
authors: GJ
authors: Zhang
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D048052:Mitogen-Activated Protein Kinase 3; D009687:Nuclear Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1; D042582:Vascular Endothelial Growth Factor C; C506487:ESR1 protein, human; C103173:TWIST1 protein, human; C508053:ERBB2 protein, human