Implication of TGF-β as a survival factor during tumour development

Transforming growth factor (TGF)-beta is a pleiotropic secretory protein which inhibits and potentiates tumour progression during early and late stage of tumourigenicity, respectively. However, it still remains veiled how TGF-beta signalling reveals its two faces. Hoshino et al. (Autocrine TGF-beta protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim, J. Biochem. 2011;149:55-65) demonstrated a new aspect of TGF-beta as a survival factor in highly metastatic breast cancer cells from which TGF-beta 1 and TGF-beta 3 are abundantly expressed. They found that TGF-beta suppressed the expression of BH3-only protein Bim which promotes programmed death signalling via release of cytochrome c from mitochondria. Further interestingly, forkhead box C1 (Foxc1) whose expression is suppressed upon TGF-beta stimulation is involved in the expression of Bim. Based on their results, autocrine TGF-beta signalling in certain breast cancers promotes cell survival via inhibition of apoptotic signalling. Thus, the inhibitors for activin receptor-like kinase (ALK)5 kinase might exert a curative influence on certain types of metastatic breast cancers.