Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells
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 k...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712001982 |
| _version_ | 1828219759424962560 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chia-Lung Tsai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:19:45Z |
| format | Article |
| id | doaj.art-19c78f11226842d99d5f4b258d590229 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T16:19:45Z |
| publishDate | 2012-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-19c78f11226842d99d5f4b258d5902292022-12-22T03:25:36ZengElsevierCell Reports2211-12472012-08-012228329310.1016/j.celrep.2012.07.002Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer CellsChia-Lung Tsai0Chi-Neu Tsai1Chiao-Yun Lin2Hsi-Wen Chen3Yun-Shien Lee4Angel Chao5Tzu-Hao Wang6Hsin-Shih Wang7Chyong-Huey Lai8Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaGraduate Institute of Clinical Medical Sciences, Chang Gung University, Kwai-Shan Taoyuan, Taiwan 333, Republic of ChinaDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaGenomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan 333, Republic of ChinaDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kwai-Shan Taoyuan Taiwan 333, Republic of ChinaStress-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.http://www.sciencedirect.com/science/article/pii/S2211124712001982 |
| spellingShingle | 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 Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells Cell Reports |
| title | Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells |
| title_full | Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells |
| title_fullStr | Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells |
| title_full_unstemmed | Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells |
| title_short | Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells |
| title_sort | secreted stress induced phosphoprotein 1 activates the alk2 smad signaling pathways and promotes cell proliferation of ovarian cancer cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712001982 |
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