TGFβ Controls Ovarian Cancer Cell Proliferation

Abstract

There have been no major improvements in the overall survival of ovarian cancer patients in recent decades. Even though more accurate surgery and more effective treatments are available, the mortality rate remains high. Given the differences in origin and the heterogeneity of these tumors, research to elucidate the signaling pathways involved is required. The Transforming Growth Factor (TGFβ) family controls different cellular responses in development and cell homeostasis. Disruption of TGFβ signaling has been implicated in many cancers, including ovarian cancer. This article considers the involvement of TGFβ in ovarian cancer progression, and reviews the various mechanisms that enable the TGFβ signaling pathway to control ovarian cancer cell proliferation. These mechanistic explanations support the therapeutic use of TGFβ inhibitors in ovarian cancer, which are currently in the early phases of development.

Prostaglandin F2α-induced TGFβ-PMEPA1 pathway is a critical mediator of epithelial plasticity and ovarian carcinoma progression

“…TGF is a crucial factor for ovarian homeostasis as well as for tumorigenesis (22). Indeed, our gene expression analysis of the TCGA TARGET GTEx patient cohort RNA sequencing data using the UCSC XENA cancer browser shows a 2-fold increase of TGFB1 mRNA levels in ovarian tumor samples, as compared to normal ovarian tissue ( fig.…”

“…The TGF- cytokine and the related signaling pathway are key players in mammalian health and disease, with an extensively studied, yet controversial role in cancer (21). Moreover, TGF- has been shown to control ovarian cancer cell proliferation (22). PMEPA1 downregulates TGF-β signaling by competing with SARA (SMAD anchor for receptor activation) for R-SMAD binding to sequester R-SMAD phosphorylation and promoting lysosomal degradation of TGF-β receptor (23).…”

A TGF-β associated genetic score to define prognosis and platinum sensitivity in advanced epithelial ovarian cancer

“…This role for TGF-b signalling pathway in the context of a dysfunctional anti-tumour immune response lead to hypothesize that TGF-b signalling inhibitors could be employed in ovarian cancer treatment, at least in a subgroup of platinum-resistant patients [33]. To further speculate, TGF-b signalling inhibitors may be used in combination with immune checkpoint inhibitors, since it has been reported that TGF-b signalling reduces tumour response to anti-PD-L1 antibodies by contributing to exclusion of T cells from the tumour microenvironment [34].…”

MSIGNET: A Bayesian Approach for Disease-associated Gene Network Identification

“…Gene functional enrichment analysis using DAVID reported the enrichment of several key pathways functioning in ovarian cancer (Supplementary Material, S4; Supplementary Table S4). For example, TGF-beta signaling pathway (p-value = 1.6e-11) plays a key role in ovarian cancer cell proliferation [27]. MAPK signaling pathway, a known pathway for cancer cell survival and usually resistant to drug therapy [28], is also enriched (p-value 3.6e-3).…”