title: Secreted stress-induced phosphoprotein 1 activates the ALK2-SMAD signaling pathways and promotes cell proliferation of ovarian cancer cells.
abstract: Stress-induced phosphoprotein 1 (STIP1), a cochaperone that organizes other chaperones, heat shock proteins (HSPs), was recently shown to be secreted by human ovarian cancer cells. In neuronal tissues, binding to prion protein was required for STIP1 to activate the ERK (extracellular-regulated MAP kinase) signaling pathways. However, we report that STIP1 binding to a bone morphogenetic protein (BMP) receptor, ALK2 (activin A receptor, type II-like kinase 2), was necessary and sufficient to stimulate proliferation of ovarian cancer cells. The binding of STIP1 to ALK2 activated the SMAD signaling pathway, leading to transcriptional activation of ID3 (inhibitor of DNA binding 3), promoting cell proliferation. In conclusion, ovarian-cancer-tissue-secreted STIP1 stimulates cancer cell proliferation by binding to ALK2 and activating the SMAD-ID3 signaling pathways. Although animal studies are needed to confirm these mechanisms in vivo, our results may pave the way for developing novel therapeutic strategies for ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kwai-Shan Taoyuan Taiwan, Republic of China.
authors.forename: Chia-Lung
authors.initials: CL
authors.lastname: Tsai
authors.forename: Chi-Neu
authors.initials: CN
authors.lastname: Tsai
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Lin
authors.forename: Hsi-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
authors.forename: Hsin-Shih
authors.initials: HS
authors.lastname: Wang
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011485:Protein Binding; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C079373:STIP1 protein, human; D051785:Smad Proteins; C075640:ID3 protein, human; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I