Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells

Duan, Liang; Ye, Liwei; Wu, Rui; Wang, Haiyan; Li, Xueru; Li, Huan; Yuan, Sun; Zha, He; Sun, Hui; Zhang, Yunyuan; Chen, Xian; Zhang, Yan; Zhou, Lan

doi:10.1002/jcb.25063

Cited by 21 publications

(22 citation statements)

References 42 publications

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“…BMP9 has been implied in tumourigenesis (7)(8)(9)(10)(11)(12)(13)16,(19)(20)(21)(22). The proliferative effect of BMP9 on tumours varies considerably.…”

Section: Discussionmentioning

confidence: 99%

“…The proliferative effect of BMP9 on tumours varies considerably. BMP9 promotes the proliferation of ovarian cancer cells (21) and hepatocellular carcinoma cells (22), but it inhibits the proliferation of colon cancer cells (19), breast cancer cells (20) and gastric cancer cells (16). However, the proliferative effect of BMP9 on OS is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies also indicated that BMP9 failed to induce osteogenic differentiation in OS (8,9,(11)(12)(13). Aberrant expression of BMP9 might result in many human tumours, such as colon cancer (19), breast cancer (20), ovarian cancer (21), hepatocellular carcinoma (22) and gastric cancer (16). These data indicate that the abnormal osteogenic differentiation related to BMP9 might be one of the determinants in the pathogenesis of OS.…”

Section: Introductionmentioning

confidence: 86%

“…BMPs play important roles in development and cellular physiology processes, such as proliferation, differentiation, apoptosis, adhesion and migration (15,16). Yang et al suggested that OS cells might be maintained in an undifferentiated state secondary to impaired TGF-β/BMP signalling (13).…”

Section: Introductionmentioning

confidence: 99%

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All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

Meng

et al. 2017

International Journal of Oncology

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Abstract. Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. However, the concomitant effect of ATRA and BMP9 in OS cells is unclear; therefore, in the present study, we focused on this topic. The results showed that BMP9 significantly promoted the proliferation of human OS 143B cells and did not induce osteogenic differentiation of cells in vitro (p<0.01). ATRA inhibited proliferation and induced osteogenesis in 143B cells; these effects could be enhanced by BMP9 overexpression (p<0.05). ATRA could significantly increase the level of phosphorylated p38 MAPK (p-p38) in 143B cells, while BMP9 did not have any significant effect. Notably, BMP9 overexpression enhanced the ability of ATRA to increase the levels of p-p38. Both the osteogenic differentiation and the anti-proliferative activity of BMP9 in the presence of ATRA decreased upon treatment with a specific inhibitor of p38 MAPK (SB203580) (p<0.01). This study indicates that the osteogenic differentiation ability of BMP9 in 143B cells can be restored by ATRA, and the combination of BMP9 and ATRA generated a stronger anti-proliferative effect on 143B cells than ATRA alone. This result may be due to the activation of the p38 MAPK pathway.

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“…BMP9 has been implied in tumourigenesis (7)(8)(9)(10)(11)(12)(13)16,(19)(20)(21)(22). The proliferative effect of BMP9 on tumours varies considerably.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

Meng

et al. 2017

International Journal of Oncology

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“…BMP-9 prevented the proliferation of HER2-positive breast cancer cells by inactivating ERK1/2 protein and repressing the PI3K/AKT signaling pathway [35]. In gastric cancer, PI3K/AKT pathway inhibition was involved in the tumor-suppressor effects of BMP-9 [121]. Similar to BMP-9, BMP-2 inhibits the growth and migration of HCC cells by attenuating the PI3K/AKT signaling pathway [34].…”

Section: Molecular Pathways Regulated By the Bmp Signaling Pathwaymentioning

confidence: 99%

BMP signaling and its paradoxical effects in tumorigenesis and dissemination

Zhang

Long

et al. 2016

Oncotarget

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Bone morphogenetic proteins (BMPs) play important roles in embryonic and postnatal development by regulating cell differentiation, proliferation, motility, and survival, thus maintaining homeostasis during organ and tissue development. BMPs can lead to tumorigenesis and regulate cancer progression in different stages. Therefore, we summarized studies on BMP expression, the clinical significance of BMP dysfunction in various cancer types, and the molecular regulation of various BMP-related signaling pathways. We emphasized on the paradoxical effects of BMPs on various aspects of carcinogenesis, including epithelial–mesenchymal transition (EMT), cancer stem cells (CSCs), and angiogenesis. We also reviewed the molecular mechanisms by which BMPs regulate tumor generation and progression as well as potential therapeutic targets against BMPs that might be valuable in preventing tumor growth and invasion.

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BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer

Wisnieski

Leal

Calcagno

et al. 2016

J of Cellular Biochemistry

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Different from genetic alterations, the reversible nature of epigenetic modifications provides an interesting opportunity for the development of clinically relevant therapeutics in different tumors. In this study, we aimed to screen and validate candidate genes regulated by the epigenetic marker associated with transcriptional activation, histone acetylation, in gastric cancer (GC). We first compared gene expression profile of trichostatin A-treated and control GC cell lines using microarray assay. Among the 55 differentially expressed genes identified in this analysis, we chose the up-regulated genes BMP8B and BAMBI for further analyses, that included mRNA and histone acetylation quantification in paired GC and nontumor tissue samples. BMP8B expression was reduced in GC compared to nontumor samples (P < 0.01). In addition, reduced BMP8B expression was associated with poorly differentiated GC (P = 0.02). No differences or histopathological associations were identified concerning BAMBI expression. Furthermore, acetylated H3K9 and H4K16 levels at BMP8B were increased in GC compared to nontumors (P < 0.05). However, reduced levels of acetylated H3K9 and H4K16 were associated with poorly differentiated GC (P < 0.05). Reduced levels of acetylated H3K9 was also associated with diffuse-type histological GC (P < 0.05). Notably, reduced BMP8B mRNA and acetylated H4K16 levels were positively correlated in poorly differentiated GC (P < 0.05). Our study demonstrated that BMP8B seems to be a tumor suppressor gene regulated by H4K16 acetylation in poorly differentiated GC. Therefore, BMP8B may be a potential target for TSA-based therapies in this GC sample subset. J. Cell. Biochem. 118: 869-877, 2017. © 2016 Wiley Periodicals, Inc.

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Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells

Cited by 21 publications

References 42 publications

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

BMP signaling and its paradoxical effects in tumorigenesis and dissemination

BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer

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