title: SHON, a novel secreted protein, regulates epithelial-mesenchymal transition through transforming growth factor-β signaling in human breast cancer cells.
abstract: The epithelial-mesenchymal transition (EMT) is one of the main mechanisms contributing to the onset of cancer metastasis, and has proven to be associated with breast cancer progression. SHON is a novel secreted hominoid-specific protein we have previously identified; it is specifically expressed in all human cancer cell lines tested and is oncogenic for human mammary carcinoma cells. Here, we show that ectopic overexpression of SHON in immortalized human mammary epithelial cells is sufficient for cells to acquire the mesenchymal traits, as well as the enhanced cell migration and invasion, along with the epithelial stem cell properties characterized by increased CD44(high) /CD24(low) subpopulation and mammosphere-forming ability. Moreover, we demonstrate that SHON positively activates the autocrine transforming growth factor-β (TGF-β) pathway to contribute to EMT, while SHON itself is induced by TGF-β in mammary epithelial cells. These data are in favor of a SHON-TGFβ-SHON-positive feedback loop that regulates EMT program in breast cancer progression. Finally, examination of the human clinic breast cancer specimens reveals that tumor cells may extracellularly release SHON protein to promote the cancerization of surrounding cells. Together, our findings define an important function of SHON in regulation of EMT via TGF-β signaling, which is closely associated with the invasive subtypes of human breast cancer.
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.forename: Jingxin
authors.initials: J
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Jiwei
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
mesh_terms: D016723:Bone Remodeling; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D015513:Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D015513:Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C000731887:SHON protein, human
keywords: EMT; SHON; TGF-β; human breast cancer