Mechanisms of TGFβ-Induced Epithelial–Mesenchymal Transition

Abstract

Transitory phenotypic changes such as the epithelial–mesenchymal transition (EMT) help embryonic cells to generate migratory descendants that populate new sites and establish the distinct tissues in the developing embryo. The mesenchymal descendants of diverse epithelia also participate in the wound healing response of adult tissues, and facilitate the progression of cancer. EMT can be induced by several extracellular cues in the microenvironment of a given epithelial tissue. One such cue, transforming growth factor β (TGFβ), prominently induces EMT via a group of specific transcription factors. The potency of TGFβ is partly based on its ability to perform two parallel molecular functions, i.e. to induce the expression of growth factors, cytokines and chemokines, which sequentially and in a complementary manner help to establish and maintain the EMT, and to mediate signaling crosstalk with other developmental signaling pathways, thus promoting changes in cell differentiation. The molecules that are activated by TGFβ signaling or act as cooperating partners of this pathway are impossible to exhaust within a single coherent and contemporary report. Here, we present selected examples to illustrate the key principles of the circuits that control EMT under the influence of TGFβ.

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

“…Conversely, when we considered “incoming” signals to malignant cells, we found that CAFs expressed notably higher numbers of ligands that correspond to receptors expressed by the malignant cells of the corresponding tumor (hypergeometric test, p<0.05; Figures 4E and S5L). These included interactions that may promote EMT, such as TGFB3-TGFBR2, FGF7-FGFR2 and CXCL12-CXCR7 (Figure 4F) (Moustakas and Heldin, 2016; Ranieri et al, 2016; Yao et al, 2016). Accordingly, when we stained tumors for CAF markers (FAP, PDPN), we found that CAFs were present near p-EMT cells at the leading edge (Figures 4C and S5M).…”

Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-&beta;/Smad2/3 signaling pathway in bladder cancer cells

“…TGF-β is known to be capable of activating the phosphorylation of Smad2 and Smad3, and plays key roles in regulating various cellular responses including cell proliferation, extracellular matrix production, and apoptosis 25,26. Recent studies have proposed that the activation of TGF-β signaling involves the EMT process and increases the potential for tumor metastasis 27–29. In addition, upregulated MMP-9 expression has been shown to enhance the invasion and migration capabilities of cancer cells in various tumors 30–32.…”

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

“…EMT is a crucial step in which epithelial cells differentiate into mesenchymal cells, and TGF-β induces EMT in various epithelial cells [37][38][39]. EMT is important in embryonic development and tissue morphogenesis, wound healing, and cancer.…”