BMP4 enhances anoikis resistance and chemoresistance of breast cancer cells through canonical BMP signaling

Sharma, Renu; Gogoi, Gayatri; Saikia, Snigdha; Sharma, Amit; Kalita, Deep Jyoti; Sarma, Anupam; Limaye, Anil Mukund; Gaur, Manish Kumar; Bhattacharyya, Jayanta; Jaganathan, Bithiah Grace

doi:10.1007/s12079-021-00649-9

Cited by 35 publications

(24 citation statements)

References 51 publications

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“…As this discrepancy is thought to be caused by the off-target effects of each inhibitor, the development of more specific ALK2 inhibitors is required ( Ali et al, 2015 ). In addition, as mentioned above, because BMPs have tumor-suppressive functions under certain conditions, tumor formation or metastasis might be promoted through the inhibition of BMP signaling ( Vollaire et al, 2019 ; Sharma et al, 2021 ). We should clarify which types of cancer ALK2 inhibitors are effective against.…”

Section: Applications Of Small-molecule Bone Morphogenetic Protein In...mentioning

confidence: 99%

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

Ehata

Miyazono

2022

Front. Cell Dev. Biol.

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Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, are multifunctional cytokines. BMPs have a broad range of functions, and abnormalities in BMP signaling pathways are involved in cancer progression. BMPs activate the proliferation of certain cancer cells. Malignant phenotypes of cancer cells, such as increased motility, invasiveness, and stemness, are enhanced by BMPs. Simultaneously, BMPs act on various cellular components and regulate angiogenesis in the tumor microenvironment. Thus, BMPs function as pro-tumorigenic factors in various types of cancer. However, similar to TGF-β, which shows both positive and negative effects on tumorigenesis, BMPs also act as tumor suppressors in other types of cancers. In this article, we review important findings published in the recent decade and summarize the pro-oncogenic functions of BMPs and their underlying mechanisms. The current status of BMP-targeted therapies for cancers is also discussed.

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Section: Applications Of Small-molecule Bone Morphogenetic Protein In...mentioning

confidence: 99%

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

Ehata

Miyazono

2022

Front. Cell Dev. Biol.

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“…NOX4 overexpression could promote anoikis resistance in gastric cancer by increasing reactive oxygen species (ROS) generation and upregulating EGFR expression, thereby enhancing the metastasis of gastric cancer ( Du et al, 2018 ). Additionally, anoikis resistance was shown to exert an important function in therapeutic resistance ( Sharma et al, 2022 ). Although anoikis plays a non-negligible role in HCC progression ( Hu et al, 2017 ; Li et al, 2019 ; Mo et al, 2020 ; Song et al, 2021 ), its prognostic value has not been systematically evaluated in HCC.…”

Section: Introductionmentioning

confidence: 99%

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

et al. 2023

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Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear.Methods: We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored.Results: ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration.Conclusion: In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.

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“…To explore more detailed mechanisms by which the activation of Wnt-β-catenin signaling enhanced cell proliferation and reduced catecholamine synthesis in PPGL cells, we examined the interaction of Wnt and BMP signaling in PC12 cells. BMPs have been reported to regulate cell growth, apoptosis, migration, and invasion in many cancers, including breast cancer, hepatocellular carcinoma, gastric cancer, lung cancer, and prostate cancer [ 12 , 13 ]. However, the function of BMPs on PPGL growth has been scarcely explored, and thus we examined the effects of BMPs on the proliferation of PPGL cells using PC12 cells.…”

Section: Resultsmentioning

confidence: 99%

Effects of Wnt-β-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells

Morimoto

Inagaki

Komatsubara

et al. 2022

Journal of the Endocrine Society

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Pheochromocytomas and paragangliomas (PPGLs) are classified into 3 major categories with distinct driver genes: pseudohypoxia, kinase signaling, and Wnt-altered subtypes. PPGLs in the Wnt-altered subtype are sporadic and tend to be aggressive with metastasis, where somatic gene fusions affecting mastermind-like 3 (MAML3) and somatic mutations in cold shock domain containing E1 (CSDE1) cause overactivation of Wnt-β-catenin signaling. However, the relation between Wnt-β-catenin signaling and the biological behavior of PPGLs remains unexplored. In rat pheochromocytoma PC12 cells, Wnt3a treatment enhanced cell proliferation and suppressed mRNA expression of tyrosine hydroxylase (TH), i.e. the rate-limiting enzyme of catecholamine biosynthesis, and dopamine secretion. We identified the expression of sclerostin in PC12 cells, which is known as an osteocyte-derived negative regulator for Wnt signaling-driven bone formation. Inhibition of endogenous Wnt pathway by XAV939 or sclerostin resulted in attenuated cell proliferation and increased TH expression. Furthermore, Wnt3a pretreatment suppressed bone morphogenetic protein (BMP)-induced Smad1/5/9 phosphorylation whereas BMPs enhanced sclerostin expression in PC12 cells. In the Wnt-altered subtype, the increased Wnt-β-catenin pathway may contribute the aggressive clinical behavior with reduced catecholamine production. Furthermore, up-regulated expression of sclerostin by BMPs may explain the osteolytic metastatic lesions observed in metastatic PPGLs.

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BMP4 enhances anoikis resistance and chemoresistance of breast cancer cells through canonical BMP signaling

Cited by 35 publications

References 51 publications

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

Effects of Wnt-β-Catenin Signaling and Sclerostin on the Phenotypes of Rat Pheochromocytoma PC12 Cells

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