Role of ACTN4 in Tumorigenesis, Metastasis, and EMT

Abstract

The actin-binding protein ACTN4 belongs to a family of actin-binding proteins and is a non-muscle alpha-actinin that has long been associated with cancer development. Numerous clinical studies showed that changes in ACTN4 gene expression are correlated with aggressiveness, invasion, and metastasis in certain tumors. Amplification of the 19q chromosomal region where the gene is located has also been reported. Experimental manipulations with ACTN4 expression further confirmed its involvement in cell proliferation, motility, and epithelial-mesenchymal transition (EMT). However, both clinical and experimental data suggest that the effects of ACTN4 up- or down-regulation may vary a lot between different types of tumors. Functional studies demonstrated its engagement in a number of cytoplasmic and nuclear processes, ranging from cytoskeleton reorganization to regulation of different signaling pathways. Such a variety of functions may be the reason behind cell type and cell line specific responses. Herein, we will review research progress and controversies regarding the prognostic and functional significance of ACTN4 for tumorigenesis.

Chromatin Accessibility Reveals Potential Prognostic Value of the Peak Set Associated with Smoking History in Patients with Lung Adenocarcinoma

“…As for the tight junction pathway, alterations in expressions of its proteins induced by smoking are involved in increased lung epithelial permeability and epithelial-mesenchymal transition (EMT), thus influencing cancer progression(Shaykhiev et al, 2011; Soini, 2012). The genes we identified through PC2-related peaks, such as ACTN4 and CLDN3 , are consistent with the important role for this pathway in LUAD oncogenesis(Zhang et al, 2017; Tentler et al, 2019). Specifically, ACTN4 amplification can be induced by smoking and is also associated with increased mortality risk among patients with early stage of LUAD(Noro et al, 2013).…”

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

“…Based on dynamic property of cell identity, different mechanisms may be involved in ensuring this feature and EMT is one of them. During EMT activation, cells lose their identity and morphology to become a new one with mesenchymal characteristics [ 49 , 50 ]. It is worth mentioning that EMT is a reversible mechanism and its converse route is known as mesenchymal-to-epithelial transition (MET) [ 51 ].…”

Machilin D, a Lignin Derived from Saururus chinensis, Suppresses Breast Cancer Stem Cells and Inhibits NF-κB Signaling

“…Machilin D inhibited the growth of breast cancer cells and mammospheres ( Figure 3). Metastasis is known to cause high rates of recurrence and mortality in cancer patients [44,45]. Machilin D inhibited the migration, invasion, and colony formation of the breast cancer cells (Figure 3).…”