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	Chia-Lung Tsai, Chi-Neu Tsai, Chiao-Yun Lin, Hsi-Wen Chen, Yun-Shien Lee, Angel Chao, Tzu-Hao Wang, Hsin-Shih Wang, Chyong-Huey Lai
Journal	Cell reports (Cell Rep) Vol. 2 Issue 2 Pg. 283-93 (Aug 30 2012) ISSN: 2211-1247 [Electronic] United States
PMID	22884369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References	Heat-Shock Proteins Inhibitor of Differentiation Proteins Neoplasm Proteins STIP1 protein, human Smad Proteins ID3 protein, human ACVR1 protein, human Activin Receptors, Type I
Topics	Activin Receptors, Type I (genetics, metabolism) Cell Line, Tumor Cell Proliferation Female Heat-Shock Proteins (genetics, metabolism) Humans Inhibitor of Differentiation Proteins (genetics, metabolism) Neoplasm Proteins (genetics, metabolism) Ovarian Neoplasms (genetics, metabolism, pathology, therapy) Protein Binding Signal Transduction Smad Proteins (genetics, metabolism)

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