title: The potential role of Brachyury in inducing epithelial-to-mesenchymal transition (EMT) and HIF-1α expression in breast cancer cells.
abstract: One of transcription factors of the T-box family, Brachyury has been implicated in tumorigenesis of many types of cancers, regulating cancer cell proliferation, metastasis, invasion and epithelial-to-mesenchymal transition (EMT). However, the role of Brachyury in breast cancer cells has been scarcely reported. The present study aimed to investigate the expression and role of Brachyury in breast cancer. Brachyury expression was analyzed by qRT-PCR and Western blot. The correlations between Brachyury expression and clinicopathological factors of breast cancer were determined. Involvement of EMT stimulation and hypoxia-inducible factor-1α (HIF-1α) expression induction by Brachyury was also evaluated. Moreover, the effect of Brachyury on tumor growth and metastasis in vivo was examined in a breast tumor xenograft model. Brachyury expression was enhanced in primary breast cancer tissues and Brachyury expression was correlated with tumor stage and lymph node metastasis. Hypoxia enhanced Brachyury expression, the silencing of which blocked the modulation effect of hypoxia on E-cadherin and vimentin expression. Brachyury significantly augmented HIF-1alpha expression via PTEN/Akt signaling as well as accelerated cell proliferation and migration in vitro. Additionally, Brachyury accelerated breast tumor xenograft growth and increased lung metastasis in nude mice. In summary, our data confirmed that Brachyury might contribute to hypoxia-induced EMT of breast cancer and trigger HIF-1alpha expression via PTEN/Akt signaling.
authors.affiliation: Department of Mammary Surgery, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Cancer Radiotherapy, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403, China. Electronic address: jingjingzhangzs@163.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Cancer Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Mammary Surgery, Zhongshan Hospital of Sun Yat-sen University, Zhongshan, 528403, China. Electronic address: feihailingfhl@163.com.
authors.forename: Feihai
authors.initials: F
authors.lastname: Ling
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005326:Fetal Proteins / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D020825:T-Box Domain Proteins / Q000502:physiology*; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C497442:HIF1A protein, human
keywords: Brachyury; Breast cancer; Epithelial-to-mesenchymal transition; Hypoxia-inducible factor-1α; Tumor xenograft