The Role of Actin Dynamics and Actin-Binding Proteins Expression in Epithelial-to-Mesenchymal Transition and Its Association with Cancer Progression and Evaluation of Possible Therapeutic Targets

Abstract

Metastasis causes death of 90% of cancer patients, so it is the most significant issue associated with cancer disease. Thus, it is no surprise that many researchers are trying to develop drugs targeting or preventing them. The secondary tumour site formation is closely related to phenomena like epithelial-to-mesenchymal and its reverse, mesenchymal-to-epithelial transition. The change of the cells' phenotype to mesenchymal involves the acquisition of migratory potential. Cancer cells movement is possible due to the development of invasive structures like invadopodia, lamellipodia, and filopodia. These changes are dependent on the reorganization of the actin cytoskeleton. In turn, the polymerization and depolymerization of actin are controlled by actin-binding proteins. In many tumour cells, the actin and actin-associated proteins are accumulated in the cell nucleus, suggesting that it may also affect the progression of cancer by regulating gene expression. Once the cancer cell reaches a new habitat it again acquires epithelial features and thus proliferative activity. Targeting of epithelial-to-mesenchymal or/and mesenchymal-to-epithelial transitions through regulation of their main components expression may be a potential solution to the problem of metastasis. This work focuses on the role of these processes in tumour progression and the assessment of therapeutic potential of agents targeting them.

Promoter Methylation-Regulated miR-145-5p Inhibits Laryngeal Squamous Cell Carcinoma Progression by Targeting FSCN1

“…These changes depend on the reorganization of actin cytoskeleton, and actin-associated proteins control the polymerization and depolymerization processes to regulate the reorganization of actin cytoskeleton. 40 , 41 Moreover, recent studies revealed that the actin binding protein Cofilin 1 ( CFL1 ) promotes the EMT process by promoting the formation of invasive structures, as well as by modulating EMT-related gene expression via regulation of actin organization in the nucleus. 42 The present results demonstrate that FSCN1 knockdown inhibits invadopodia formation and impairs actin cytoskeleton organization.…”

Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome

“…Taken together, our study reveals a novel relationship between nuclear actin and HGPS. Recent research has shown that nuclear actin is involved in multiple diseases, including cancer and myopathy [60,61]. Understanding the molecular mechanisms of nuclear actin in diseases by using model systems could contribute to the possibility of using known actin-binding chemicals for therapeutic purposes.…”

The effect of piperlongumine on endothelial and lung adenocarcinoma cells with regulated expression of profilin-1

“… 3 – 5 Furthermore, in the recent years, there is also an increase of interests in actin-binding proteins (ABPs) in the different types of cells, especially in the context of cell death, migration, or cell junction stabilization. 6 – 8 ABPs family is the group of various proteins involved in the regulation of actin filaments’ stability, growth and disassembly (polymerization and depolymerization). 9 , 10 One of the examples of ABPs is profilin-1 (PFN1), the protein involved in actin assembly through the exchange of ADP for ATP on G-actin and transport of profilin–actin complex to barbed ends of actin filaments.…”