TRIM37 promotes epithelial-mesenchymal transition in colorectal cancer

Ding

et al. 2020

Preprint

Abstract Background Emerging evidence shows that the deregulation of tripartite motif (TRIM) family proteins have various functions in cellular processes and play important role in innate immunity, nervous system diseases, protein quality control and carcinogenesis. However, the precise biological function and molecular mechanism of TRIM family proteins in ovarian cancer chemo-resistance remain unclear. Methods The protein and mRNA expression of TRIM37 in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot and IHC respectively. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM37 in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37 promotes chemoresistance in ovarian cancer cells. Results Herein, we found that the protein and mRNA expression of TRIM37 were markedly overexpressed in ovarian cancer tissues which shown partially responded to cisplatin chemotherapy. Moreover, TRIM37 expression was inversely correlated with patient survival in our cohort HCC tissue samples and public HCC database. Overexpression of TRIM37 confers cisplatin resistance on ovarian cancer cells; but, inhibition of TRIM37 sensitized ovarian cancer cell lines to cisplatin cytotoxicity both in vitro and in vivo. Additionally, TRIM37 upregulated the levels of nuclear β-catenin, thereby activating canonical wnt/β-catenin signaling. Conclusions our results demonstrate that targeting TRIM37/β-catenin axis may represent a promising strategy to enhance cisplatin response in patients with chemo-resistant ovarian cancer.

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Tripartite Motif Containing 37 Activates the Wnt/β-catenin Signalling Pathway and Confers Cisplatin Resistance to Ovarian Carcinoma

Ding

et al. 2020

Preprint

The Journal of Pathology

“…TRIM37, a member of this family, is reported to be involved in tumorigenesis and to function as an oncoprotein . The expression of TRIM37 has been associated with poor prognosis in several types of tumors, including colorectal cancer , pancreatic cancer , and hepatocellular carcinoma . In particular, overexpression of TRIM37 could promote cell proliferation and migration in HCC .…”

Section: Introductionmentioning

confidence: 99%

Tripartite motif‐containing 37 (TRIM37) promotes the aggressiveness of non‐small‐cell lung cancer cells by activating the NF‐κB pathway

Deng

Zhao

et al. 2018

Non-small-cell lung cancer (NSCLC), in which the NF-κB pathway is constitutively activated, is one of the most common malignancies. Herein, we identify an E3 ubiquitin ligase, tripartite motif-containing 37 (TRIM37), participating in the K63 polyubiquitination of TRAF2, which is a significant step in the activation of NF-κB signaling. Both the mRNA and the protein expression levels of TRIM37 were much higher in NSCLC cell lines and tissues than in normal bronchial epithelial cells and matched adjacent non-tumor tissues. TRIM37 expression correlated closely with clinical stage and poor survival in NSCLC. Overexpression of TRIM37 antagonized cisplatin-induced apoptosis, induced angiogenesis and proliferation, and increased the aggressiveness of NSCLC cells in vitro and in vivo, whereas inhibition of TRIM37 led to the opposite effects. Gene set enrichment analysis (GSEA) showed that TRIM37 expression significantly correlated with NF-κB signaling. Furthermore, we found that TRIM37 bound to TRAF2 and promoted K63-linked ubiquitination of TRAF2, sustaining the eventual activation of the NF-κB pathway. Mutation in the ring finger domain of TRIM37, a hallmark of E3 ubiquitin ligases, led to loss of the ability to promote K63 polyubiquitination of TRAF2 and activate NF-κB signaling. Taken together, our findings provide evidence that TRIM37 plays an important role in constitutive NF-κB pathway activation and could serve as a prognostic factor and therapeutic target in NSCLC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

“…It was recently reported to be a critical mediator of cell metastasis in medulloblastoma, engaging the PI3K/Akt signaling pathway to induce EMT and to promote cell migration and invasion,65 which are characteristics of the CSC population. TRIM37 (a class VIII member with C-terminal MATH domain) also promotes EMT in cancer cells by activation of Wnt/β-catenin signaling.Colorectal cancer cells that overexpress TRIM37 are more aggressive, with higher tumorigenicity and increased migratory and invasive capabilities,66 suggesting a possible role for TRIM37 in stemness acquisition. However, some of the TRIM members are known tumor suppressors.…”

mentioning

confidence: 99%

The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

et al. 2019

The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. The members of this family are characterized by an N-terminal TRIM motif containing one RING-finger domain, one or two zinc-finger domains called B boxes (B1 box and B2 box), and a coiled-coil region.The TRIM motif can be found in isolation or in combination with a variety of C-terminal domains, and based on C-terminus, TRIM proteins are classified into 11 distinct groups.Because of the complex nature of TRIM proteins, they are implicated in a variety of cellular functions and biological processes, including regulation of cell proliferation, cell division and developmental processes, cancer transformation, regulation of cell metabolism, autophagocytosis, modification of chromatin status, regulation of gene transcription, post-translational modifications, and interactions with pathogens. Here, we demonstrate the specific activities of TRIM family proteins that contribute to the cancer stem cell phenotype. A growing body of evidence demonstrates that several TRIM members guarantee the acquisition of stem cell properties and the ability to sustain stem-like phenotype by cancer cells using distinct mechanisms. For other members, further work is needed to understand their full contribution to stem cell self-renewal.Identification of TRIM proteins that possess the potential to serve as therapeutic targets may result in the development of new therapeutic strategies. Finally, these strategies may result in the disruption of the machinery of stemness acquisition, which may prevent tumor growth, progression, and overcome the resistance to anticancer therapies. K E Y W O R D Scancer, pluripotency, RING, self-renewal, stem cells, TRIM