Cytoskeletal Proteins in Cancer and Intracellular Stress: A Therapeutic Perspective

Abstract

Cytoskeletal proteins, which consist of different sub-families of proteins including microtubules, actin and intermediate filaments, are essential for survival and cellular processes in both normal as well as cancer cells. However, in cancer cells, these mechanisms can be altered to promote tumour development and progression, whereby the functions of cytoskeletal proteins are co-opted to facilitate increased migrative and invasive capabilities, proliferation, as well as resistance to cellular and environmental stresses. Herein, we discuss the cytoskeletal responses to important intracellular stresses (such as mitochondrial, endoplasmic reticulum and oxidative stresses), and delineate the consequences of these responses, including effects on oncogenic signalling. In addition, we elaborate how the cytoskeleton and its associated molecules present themselves as therapeutic targets. The potential and limitations of targeting new classes of cytoskeletal proteins are also explored, in the context of developing novel strategies that impact cancer progression.

Survival Pathways Are Differently Affected by Microgravity in Normal and Cancerous Breast Cells

“…CSK changes are instrumental in driving progressive modifications in cell shape, and some of these architectural alterations play a pivotal role in triggering a wide range of death processes, including apoptosis and anoikis [ 17 ]. Accordingly, in recent decades, the drug-mediated interference with CSK remodeling has been actively pursued to find a successful strategy of cancer treatment [ 18 ]. Therefore, we explored CSK changes in both MCF10A and MCF-7 cells in microgravity.…”

Expression of palladin is associated with disease progression in metastatic high‐grade serous carcinoma

“…As is the case for other cellular functions, this system is deregulated in cancer cells, resulting in enhanced migration and invasion, proliferation and cell survival, and resistance to stress, including chemotherapy. 1 Deregulation of the cytoskeleton network is closely related to epithelial-mesenchymal transition, in which expression levels of cytoskeleton components, cell form and motility are affected. 2 Actin microfilaments are central regulators of motility, migration and invasion through regulation of phosphatydilinositol-3-kinase (PI3K) pathway signalling, secretion of enzymes modifying the tumour microenvironment and production of reactive oxygen species.…”

“…2 Actin microfilaments are central regulators of motility, migration and invasion through regulation of phosphatydilinositol-3-kinase (PI3K) pathway signalling, secretion of enzymes modifying the tumour microenvironment and production of reactive oxygen species. 1 Palladin is member of a family of actin-associated cytoplasmic proteins that additionally includes myopalladin and myotilin. All members contain immunoglobulin-like domains providing rigidity and correct spacing to the protein.…”

“…The cell cytoskeleton, consisting of microtubules, intermediate filaments and microfilaments, regulates cell structure, adhesion, motility and cellular trafficking under normal conditions. As is the case for other cellular functions, this system is deregulated in cancer cells, resulting in enhanced migration and invasion, proliferation and cell survival, and resistance to stress, including chemotherapy 1 . Deregulation of the cytoskeleton network is closely related to epithelial‐mesenchymal transition, in which expression levels of cytoskeleton components, cell form and motility are affected 2 …”

Cell properties assessment using optimized dielectrophoresis-based cell stretching and lumped mechanical modeling

“…For example, Malaria inducing Plasmodium falciparum increases the cytoplasm's stiffness noticeably by producing inert crystals of hemozoin 3 . Also, the cell's biomechanical properties are impacted by cancer and chemotherapy, for instance, affecting the polymerization of microtubule filaments and hence markedly influencing the cytoskeletal stiffness 4 . Furthermore, during epithelial-mesenchymal transitions (EMTs), cytoskeleton, and, consequently, overall cell biomechanics experience a remarkable change 5 .…”