Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Abstract

Epithelial to mesenchymal transition (EMT) contributes to tumor progression, cancer cell invasion, and therapy resistance. EMT is regulated by transcription factors such as the protein products of the SNAI gene family, which inhibits the expression of epithelial genes. Several signaling pathways, such as TGF-beta1, IL-6, Akt, and Erk1/2, trigger EMT responses. Besides regulatory transcription factors, RNA molecules without protein translation, micro RNAs, and long non-coding RNAs also assist in the initialization of the EMT gene cluster. A challenging novel aspect of EMT research is the investigation of the interplay between tumor microenvironments and EMT. Several microenvironmental factors, including fibroblasts and myofibroblasts, as well as inflammatory, immune, and endothelial cells, induce EMT in tumor cells. EMT tumor cells change their adverse microenvironment into a tumor friendly neighborhood, loaded with stromal regulatory T cells, exhausted CD8+ T cells, and M2 (protumor) macrophages. Several EMT inhibitory mechanisms are instrumental in reversing EMT or targeting EMT cells. Currently, these mechanisms are also significant for clinical use.

TSPAN1: A Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance

“…In this line of evidence, tumors formed by slowly growing resistant cells JHU029-R showed a fusocellular pattern compared to parental JHU029 cells. Such pattern is associated with EMT features, which are typically prominent in aggressive and resistant tumor phenotypes [46]. Moreover, in tumors formed by resistant JHU029-R cells, TSPAN1 inhibition was able to revert the fusocellular pattern to an epithelial morphology and reduce metastasis capacity of these resistant HNSCC cells.…”

Fusobacterium nucleatum Accelerates the Progression of Colitis-Associated Colorectal Cancer by Promoting EMT

“…Cancer stemness (CS) along with EMT is known to be central to inducing metastasis in various cancers [ 19 , 20 , 21 ]. We hypothesized that F. nucleatum would enhance the stemness of CRC cells.…”

A Marine Collagen-Based Biomimetic Hydrogel Recapitulates Cancer Stem Cell Niche and Enhances Progression and Chemoresistance in Human Ovarian Cancer

“…Multiple lines of evidence have established that epithelial–mesenchymal transition (EMT) is vital in tumor growth, progression, invasion, dissemination, metastasis, and drug resistance [ 39 , 40 ]. The three-dimensional culture in MC-B hydrogels strikingly upregulated the expression of the pivotal EMT transcription factors Snail, Slug, and Twist by 163.0-fold ( p < 0.001), 109.3-fold ( p < 0.001), and 130.9-fold ( p < 0.001), respectively, compared with that of the 2D culture ( Figure 10 A).…”

“…The molecular mechanisms underlying the acquisition of chemoresistance coordinated by Notch signaling are believed to involve the induction of the EMT, the formation of tumor stem cells, and the upregulated expression of MDR such as the MDR1 and MRP1 [ 21 , 113 , 114 , 115 ]. EMT is associated with metastasis, as well as with the generation and maintenance of CSCs, contributing to tumor invasion, heterogeneity, and chemoresistance [ 39 , 40 ]. Thus, many researchers are striving to develop targeted therapeutic strategies to inhibit the Notch pathway, EMT-driving transcription factors, and cancer stemness-related molecules for the successful treatment of human malignancies.…”