Harnessing Carcinoma Cell Plasticity Mediated by TGF-β Signaling
Xuecong Wang, Jean Paul Thiery
Abstract
Epithelial cell plasticity, a hallmark of carcinoma progression, results in local and distant cancer dissemination. Carcinoma cell plasticity can be achieved through epithelial-mesenchymal transition (EMT), with cells positioned seemingly indiscriminately across the spectrum of EMT phenotypes. Different degrees of plasticity are achieved by transcriptional regulation and feedback-loops, which confer carcinoma cells with unique properties of tumor propagation and therapy resistance. Decoding the molecular and cellular basis of EMT in carcinoma should enable the discovery of new therapeutic strategies against cancer. In this review, we discuss the different attributes of plasticity in carcinoma and highlight the role of the canonical TGFβ receptor signaling pathway in the acquisition of plasticity. We emphasize the potential stochasticity of stemness in carcinoma in relation to plasticity and provide data from recent clinical trials that seek to target plasticity.