Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Abstract

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells—highlight some future perspectives in cancer therapy by targeting cytoskeleton.

Actin Cytoskeleton Dynamics and Type I IFN-Mediated Immune Response: A Dangerous Liaison in Cancer?

“…Notably, ROCK1/ROCK2 inhibitor Y-276432, which prevents MDA-MB-231 breast cancer cell metastasis, and MRCK inhibitor BDP5290 which impairs human squamous cell carcinoma invasion, have been investigated [ 43 , 44 ]. However, actin cytoskeletal dynamics as cancer therapeutic targets are not the focus of this review and are excellently reviewed elsewhere [ 5 ].…”

“…Similar to viral infection, cancer progression is governed by actin cytoskeleton modification of tumor cells, as clearly demonstrated during epithelial-mesenchymal transition (EMT) process. Epithelial cells undergo a cellular transformation and acquire motility and invasive ability, via invadopodia, lamellipodia, and filopodia, whose function strictly depends on the rearrangements of actin filaments [ 5 ]. A still growing body of evidence demonstrates that actin dynamics represent a platform for signaling pathways governing cancer progression [ 6 ], as evidenced during EMT.…”

Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins, DAAM1 and PREP, in Human Testicular Disorders

“…One of the major key events occurring during the neoplastic transformation, differentiation, and proliferation is the modification of cell shapes and their loss of polarity, determined by changes in the fundamental cytoskeletal proteome. Thus, the cytoskeleton, as well as the countless associated proteins, plays a pivotal role in this dynamic process [ 20 ].…”

CRMP2 as a Candidate Target to Interfere with Lung Cancer Cell Migration

“…Therefore, drugs that depolymerize microtubules, such as Vinca alkaloids, or stabilize them as taxanes, have been proposed as potent anticancer agents [6]. These drugs can arrest aberrant cell division [7] and metastasis [8].…”