Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis

Abstract

Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.

Prolargin and matrix metalloproteinase‐2 in heart failure after heart transplantation and their association with haemodynamics

“…19 Interestingly, smad3 signalling mediates TGFβ1-induced CTGF expression and is essential for the pathogenesis of cardiac remodelling. 44,45 In the present study, given that decorin levels were high in severe HF patients compared with controls and decreased following HT, a decrease that was associated with improvement in MRAP, LVSWI, and NT-proBNP, it is reasonable to hypothesize that higher levels of plasma decorin may have a cardioprotective role in HF by inhibiting the profibrotic activity of TGFβ and its effector CTGF, possibly in a smad3-dependent manner, attenuating adverse cardiac remodelling.…”

Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases

“…It was reported that CTGF could positively mediate apoptosis in ovarian low-grade serous carcinoma and MCF-7, a breast cancer cell line 120 , 121 . However, in human Tenon capsule fibroblasts and chicken embryo fibroblasts, CTGF was found to negatively mediate the apoptosis 122 , 123 .…”

Downregulation of TGF-β1 suppressed proliferation and increased chemosensitivity of ovarian cancer cells by promoting BRCA1/Smad3 signaling

“…Transforming growth factor beta (TGF-β) plays an important role in promoting cell proliferation and cell cycle regulation in early oncogenesis and normal tissue development [10, 11]. Previous studies have found that TGF-β1 can activate both SMAD2 and SMAD3 [12]. SMAD2 and 3 dimerize, forming the SMAD2/3 complex.…”