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.

Keywords: calponin homology domain; colorectal cancer; metastasis; molecular targets; signaling pathways; transgelins.

FIGURE 1

Structural characteristics of transgelin. (A) Human transgelin consists of three regions: an N-terminal calponin-homolog (CH)-domain, an actin-binding motif (ABM), and a C-terminal calponin-like repeated (CLR)-region. The CH domain binds to ERK, the ABM domain binds to actin, and the C-terminal CLR domain binds to ezrin (Yin et al., 2019). Potential phosphorylation sites amino acids number 8, 11, 83, 84, 145, 163, 180, 185, 190, and 192 in T-2. (B) The tertiary fold of the CH domain (PDB: 1H67). The CH domain contains six α-helices, in which two short helical structures (II and V) and a core of four α-helices (I, III, IV, and VI) are present. Helices III and VI are approximately parallel, while helix IV is lying oblique to the other helices (Yin et al., 2020). The 3D view of the structural model was generated from the data file from the Protein Data Bank.

FIGURE 2

Signaling pathways involved in transgelin.