Attenuation of Smad2 activity shows resistance to TGF‐β signalling in mammary adenocarcinoma (MCF‐7) cells

Abstract

Transforming growth factor-β (TGF-β) is a potent inhibitor of the growth of normal mammary epithelial cells, and has a pleiotropic, context-dependent, concentration-dependent action. We found attenuation of TGF-β signalling in mammary adenoma carcinoma cells. Phosphorylation at the linker site of Smad2 occurred in a cooperative way during the attenuation of TGF-β signalling, and was associated with upregulation of CDK2 and cyclin D1. CDK2 inhibitor restored the anti-proliferative effect of TGF-β by upregulating p21, with inhibition of linker phosphorylation of Smad2. CDK2-mediated linker phosphorylation of Smad2 may be a plausible mechanism for the attenuation of TGF-β signalling in breast cancer.

TGF-beta induced RBL2 expression in renal cancer cells by down-regulating miR-93

“…They are induced by TGF-beta and result in cell cycle arrest through associating with their target cyclin-CDK complexes [3]. However, in many cancers, the cancer cells are resistant to the inhibitory effects of TGF-beta [4][5][6]. Instead of inhibiting growth, TGF-beta promotes tumor malignance and invasion [7].…”

Mechanism Analyses for Elucidating the Role of LOXL2 Silencing in Hepatocellular Carcinoma

“…Additionally, as a member of the transforming growth factor β family, TGF-β works as a multi-functional cytokine and plays an important role in cell proliferation, apoptosis and differentiation [29]. TGF-β is an important gene that has been identified as a cancer susceptibility gene that exerts tumor-suppressive effects that cancer cells must elude for malignant evolution [29][30][31][32]. TGFBR1 and TGFBR2-two transmembrane serine/threonine kinase receptors, are required for TGF-β signaling transduction.…”

Flaming the fight against cancer cells: the role of microRNA-93

“…It is held that miR-93-3p enhances the malignancy of ccRCC cells by stimulation of angiogenesis through down-regulation of PEDF [209]. Although it has been shown that TGF-β contributes to the induction of cell cycle arrest, accumulating data demonstrates that the resistance of cancer cells into TGF-β reverses its anti-tumor impact and this signaling pathway may enhance the progression of tumor cells [268][269][270][271][272]. The fundamental pathway involved in this function is various among different cancer types [273].…”