Osteopontin promotes ovarian cancer progression and cell survival and increases HIF-1alpha expression through the PI3-K/Akt pathway.
Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated glycoprotein that is overexpressed in many advanced cancers. However, the functional mechanisms by which OPN contributes to the development of ovarian cancer are poorly understood. Here, we reveal that acquired expression of OPN by HO-8910 ovarian cancer cells greatly promoted the progression of ovarian cancer. OPN expression dramatically increased the colony formation of ovarian cancer cells in vitro and tumor growth in vivo. Under the stress induced by serum depletion or curcumin treatment, OPN expression promoted the survival of ovarian cells through preventing stress-induced apoptosis. At the molecular level, both endogenous and exogenous OPN expression activated the PI3-K/Akt survival pathway and dramatically decreased p53 expression under serum depletion. In addition, HIF-1alpha was induced in OPN-producing cells under normoxia. Furthermore, we also found that inhibition of the PI3-K/Akt pathway attenuated OPN-mediated HIF-1alpha up-regulation in ovarian cancer cells. Taken together, these results indicate that OPN can increase the survival of ovarian cancer cells under stress conditions in vitro and promote the late progression of ovarian cancer in vivo, and the survival-promoting functions of OPN are mediated through Akt activation and the induction of HIF-1alpha expression.
Song
Gang
G
The Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, China.
Cai
Qiu-Feng
QF
Mao
Yu-Bin
YB
Ming
Yan-Lin
YL
Bao
Shi-Deng
SD
Ouyang
Gao-Liang
GL
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D002999:Clone Cells; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018450:Disease Progression; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011994:Recombinant Proteins; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt