Role of the focal adhesion protein TRIM15 in colon cancer development

Abstract

The tripartite motif containing (TRIM) proteins are a large family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation, and signaling pathways. Here, we show that TRIM15 co-localized to focal adhesions through homo-dimerization and significantly suppressed cell migration. Domain mapping analysis indicated that B-box2 and PRY domains were essential for TRIM15 localization to focal adhesions and inhibition of cell migration. Our protein-protein interaction screen of TRIM15 with the integrin adhesome identified several TRIM15 interacting proteins including coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. TRIM15 expression was tissue-restricted and downregulated in colon cancer. Level of TRIM15 expression was associated with colon cancer cell migration, as well as both in vitro and in vivo tumor growth. These data provide novel insights into the role of TRIM15 as an additional component of the integrin adhesome, regulating cell migration, and suggest that TRIM15 may function as a tumor suppressor of colon cancer.

TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits apoptosis in colon cancer

“…For example, TRIM24 is an oncogenic transcriptional activator in prostate cancer [30]. TRIM15 expression is decreased in human colon adenocarcinoma compared with normal colon tissues; restoring expression in CC cells suppressed tumor growth in mice [31]. Our data shows that overexpression of TRIM11 promoted CC cell proliferation and inhibited apoptosis; in contrast, knockdown of TRIM11 using CRISPR/Cas9-mediated gene editing technology suppressed cell proliferation and induced apoptosis.…”

TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway

“…Recently, TRIM proteins have been identified as important regulators of cellular processes in a variety of human cancers (21), and various TRIM proteins have been found to be highly expressed in CRC (9,22). Although the oncogenic effect of TRIM59 on progression has been confirmed in various cancers, including gastric cancer (12), osteosarcoma (23), lung (13) and cervical cancer (24), the expression and function of TRIM59 in CRC remain unclear.…”

“…Over the last decade, the role of TRIM proteins in innate immunity has been extensively studied. In addition, recent studies have shown that various members of this family, including TRIM15, TRIM25 and TRIM29, have vital roles in human tumorigenesis (9–11). …”

TRIM26 functions as a novel tumor suppressor of hepatocellular carcinoma and its downregulation contributes to worse prognosis

“…Many members of the TRIM family are revealed to be important regulators of carcinogenesis by targeting their various substrates including cell cycle regulators, checkpoint molecules, apoptosis-related factors and tumor-promoting or inhibitory factors [18,19]. For example, TRIM15 in colon cancer [20], TRIM62 in breast cancer [21] and TRIM3 in glioma [7]. TRIM proteins also play important roles in HCC.…”