The roles of TGF-β signaling in carcinogenesis and breast cancer metastasis

Abstract

Transforming growth factor-β (TGF-β) ligand is a multifunctional growth factor that regulates various cell behavior, such as cell proliferation, differentiation, migration, and apoptosis. Because TGF-β is a potent growth inhibitor, abnormalities in TGF-β signaling result in carcinogenesis. In addition to tumor suppressor function, TGF-β acts as an oncogenic factor. In particular, TGF-β signaling plays an important role during metastasis of breast cancer. Recently, epithelial-mesenchymal transition (EMT) has been shown to confer malignant properties such as cell motility and invasiveness to cancer cells and plays crucial roles during cancer metastasis. Moreover, breast stem-like cells exhibit EMT properties. Because TGF-β is a potent regulator of EMT as well as cell stemness, TGF-β signaling might play a crucial role in the regulation of breast cancer stem cells.

The T-Box transcription factor 3 in development and cancer

“…The TGF-β growth factor cytokine family is composed of a large number of secreted polypeptides that activate cellular responses involved in development, homeostasis and the immune system (92). In addition, TGF-β1 signalling has been widely reported to have a dual role in the progression of cancer.…”

“…In addition, TGF-β1 signalling has been widely reported to have a dual role in the progression of cancer. While it acts as a tumour suppressor and inhibits cell proliferation during the early stages of carcinogenesis, it promotes migration and metastasis in the late stages of the disease (92). Similar to TBX3, TGF-β1 signalling is critical for the development of the mammary glands but also contributes to breast cancer progression through the inhibition of cell proliferation and promotion of migration (93).…”

Expressional Alterations of Versican, Hyaluronan and Microfibril Associated Proteins in the Cancer Microenvironment

“…In the advanced stage of carcinogenesis, TGF-acts as an oncogenic factor and induces invasion-associated epithelial-mesenchymal transition. TGF-is thought to enhance tumor growth and invasion through regulation of immune functions and angiogenesis, as well as the production of stromal components [42]. TGF-is secreted as a latent complex containing one of the LTBPs.…”

TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer

“…While TGFβ1 inhibits cell growth at an early stage of carcinogenesis, it supports metastasis formation in late‐stage cancer (Imamura et al ., 2012). We have previously shown that TGFβ signaling and TGFβ receptor type‐2 (TGFBR2) seem to have a tumor promoting role in human estrogen receptor (ER)‐negative breast cancer (Keklikoglou et al ., 2012).…”