title: Inactivation of the phosphatidylinositol 3-kinase/Akt pathway is involved in BMP9-mediated tumor-suppressive effects in gastric cancer cells.
abstract: Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily signaling factors. Expression of several BMPs (BMP2, BMP4, and BMP7) is correlated to poor prognosis in gastric cancer patients. The function of BMP9, the latest discovered and most powerful osteogenetic factor, in gastric cancer is relatively unclear. In this report, we investigated the expression, function and underlying molecular mechanisms of BMP9 in gastric cancer. The results show that BMP9 expression was markedly decreased in gastric cancer tissues and cell lines. Enforced BMP9 expression in the gastric cancer cell lines SGC-7901 and MNK-45 increased apoptosis and reduced viability and migration. The in vivo function of BMP9 was evaluated in a xenograft mouse model. Tumors derived from SGC-7901 cells with enforced BMP9 expression (SGC-7901/BMP9) showed significantly reduced size and weight compared to that from control cells. Enforced BMP9 expression resulted in decreased Akt activity shown as lower levels of phosphorylation at Ser473 and Thr308 in Akt. The PI3K/Akt inhibitor LY294002 potentiated BMP9's viability and migration suppression, and apoptosis induction, which was associated with reduced expression of snail and VEGF and increased expression of E-cadherin. In addition, tumors derived from SGC-7901/BMP9 showed reduced Akt activity and VEGF expression, and increased E-cadherin expression. Therefore, our studies reveal for the first time that inhibition of the PI3K-Akt pathway is involved in the tumor suppressor effects of BMP9 in gastric cancer.
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
authors: Liang
authors: L
authors: Duan
authors: Liwei
authors: L
authors: Ye
authors: Rui
authors: R
authors: Wu
authors: Haiyan
authors: H
authors: Wang
authors: Xueru
authors: X
authors: Li
authors: Huan
authors: H
authors: Li
authors: Shimei
authors: S
authors: Yuan
authors: He
authors: H
authors: Zha
authors: Hui
authors: H
authors: Sun
authors: Yunyuan
authors: Y
authors: Zhang
authors: Xian
authors: X
authors: Chen
authors: Yan
authors: Y
authors: Zhang
authors: Lan
authors: L
authors: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002867:Chromones / Q000494:pharmacology; D055427:Growth Differentiation Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D002867:Chromones; D055427:Growth Differentiation Factor 2; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: APOPTOSIS; BONE MORPHOGENIC PROTEINS 9; GASTRIC CANCER; MIGRATION; VIABILITY