Question

In the lectures you heard “Cancer cells hijack the EMT process”. The definition of hijack according to the Cambridge dictionary is “to take control of or use something that does not belong to you for your own advantage”. Now, explain what does it mean when you say cancer cells hijack the EMT process or in other words, how are the cancer cells hijacking the EMT process? (5 points)

Answer 1

The epithelial-to-mesenchymal transition (EMT) takes place during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing. It is a dynamic process, by virtue of which epithelial cells can convert into a mesenchymal phenotype. However, it is also involved in tumor progression with metastatic expansion, and the generation of tumor cells with stem cell properties that play a major role in resistance to cancer treatment.

EMT is not finished in cancer cells, and tumor cells are in multiple transitional states and express a mixed epithelial and mesenchymal genes. Hybrid cells in partial EMT can move collectively as clusters, and can be more aggressive than cells with a complete EMT phenotype. EMT is also reversible by the mesenchymal-to-epithelial transition (MET), thought to affect circulating cancer cells when they reach a desirable metastatic niche to develop secondary tumors.

Metastasis requires invasion, which is enabled by EMT. Carcinoma cells in a primary tumor lose cell-cell adhesion mediated by E-cadherin repression and break through the basement membrane with increased invasive properties, and enter the bloodstream through intravasation. When these circulating tumor cells (CTCs) exit the bloodstream to form micro-metastases, they undergo MET for clonal outgrowth at these metastatic sites. Thus, EMT and MET form the initiation and completion of the invasion-metastasis cascade. At this new metastatic site, the tumor may undergo other processes to optimize growth. For eg. EMT has been associated with PD-L1 expression, particularly in lung cancer. Increased levels of PD-L1 suppresses the immune system which allows the cancer to spread more easily.