Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Abstract

Transgelins, including transgelin-1 (T-1), transgelin-2 (T-2), and transgelin-3 (T-3), are a family of actin-binding proteins (ABPs) that can alter the structure and morphology of the cytoskeleton. These proteins function by regulating migration, proliferation and apoptosis in many different cancers. Several studies have shown that in various types of tumor cells, including colorectal cancer (CRC) cells, and in the tumor microenvironment, the expression and biological effects of transgelins are diverse and may transform during tumor progression. Previous researches have demonstrated that transgelin levels are positively correlated with metastasis in CRC, and down-regulating their expression can inhibit this process. In advanced disease, T-1 is a tumor activator with increasing expression, and T-2 expression increases with the progression of CRC. Finally, T-3 is only expressed in neurons and is not associated with CRC. This evidence suggests that T-1 and T-2 are potential biomarkers and therapeutic targets for CRC metastasis.

Diversification of the calponin family proteins by gene amplification and repeat expansion of calponin‐like motifs

“…The calponin family proteins (Figure 1a) including calponin, transgelin (also known as SM22, NP25, Mp20, or myophilin), and UNC-87, bind to actin filaments and regulate actin filament stability and actomyosin contractility (Assinder, Stanton, & Prasad, 2009;Carmichael, Winder, Walsh, & Kargacin, 1994;Dvorakova, Nenutil, & Bouchal, 2014;Liu, Zhang, Li, & Wang, 2020;Rozenblum & Gimona, 2008;Winder & Walsh, 1996). Calponin was originally isolated from chicken gizzard smooth muscle as a candidate regulator of contraction with a troponin-like function (Takahashi, Hiwada, & Kokubu, 1986;Takahashi, Hiwada, & Kokubu, 1988).…”

“…The interpretation of the phenotypes is complicated by the presence of multiple calponin isoforms and calponin-related proteins, which may have overlapping roles in muscle contractility. Mammals have three calponin genes (CNN1, CNN2, and CNN3) (Liu & Jin, 2016) and three transgelin genes (TAGLN, TAGLN2, and TAGLN3) (Liu et al, 2020). Calponin-2 (CNN2) is also expressed in smooth muscle (Hossain, Hwang, Huang, Sasaki, & Jin, 2003), but either single deletion of CNN2 or double deletion of CNN1 and CNN2 in mice still causes only modest alterations in smooth muscle contractility (Feng, Wang, Takahashi, & Jin, 2019).…”

“…In cultured cells, transgelin-1/SM22α is associated with actin filaments and still allows dynamic cytoskeletal remodeling, whereas calponin is associated with actin filaments and inhibits cytoskeletal remodeling (Gimona et al, 2003). Although transgelins are implicated in actin filament stabilization (Gheorghe et al, 2008;Goodman et al, 2003;Na et al, 2015;Shapland, Hsuan, Totty, & Lawson, 1993), transgelinassociated actin filaments may still undergo turnover to support dynamic actin-dependent events such as cell migration (Liu et al, 2020).…”

Differential Expression of Drosophila Transgelins Throughout Development

“…Transgelins encompass an actin-binding protein family, well-conserved from yeast to human, implicated in cytoskeleton remodeling (Shapland et al, 1988;Assinder et al, 2009;Liu et al, 2020).…”

“…Transgelins encompass an actin-binding protein family, well-conserved from yeast to human, implicated in cytoskeleton remodeling ( Shapland et al, 1988 ; Assinder et al, 2009 ; Liu et al, 2020 ). Transgelin’s name was coined by its ability to induce actin gelation in vitro ( Shapland et al, 1993 ), while subsequent studies revealed actin filament bundling activity and its role in cellular contractility ( Han et al, 2009 ).…”