Abstract
Colorectal cancer (CRC) is one of the most frequently diagnosed tumor in humans and one of the most common causes of cancer-related death worldwide. The pathogenesis of CRC follows a multistage process which together with somatic gene mutations is mainly attributed to the dysregulation of signaling pathways critically involved in the maintenance of homeostasis of epithelial integrity in the intestine. A growing number of studies has highlighted the critical impact of members of the tripartite motif (TRIM) protein family on most types of human malignancies including CRC. In accordance, abundant expression of many TRIM proteins has been observed in CRC tissues and is frequently correlating with poor survival of patients. Notably, some TRIM members can act as tumor suppressors depending on the context and the type of cancer which has been assessed. Mechanistically, most cancer-related TRIMs have a critical impact on cell cycle control, apoptosis, epithelial–mesenchymal transition (EMT), metastasis, and inflammation mainly through directly interfering with diverse oncogenic signaling pathways. In addition, some recent publications have emphasized the emerging role of some TRIM members to act as transcription factors and RNA-stabilizing factors thus adding a further level of complexity to the pleiotropic biological activities of TRIM proteins. The current review focuses on oncogenic signaling processes targeted by different TRIMs and their particular role in the development of CRC. A better understanding of the crosstalk of TRIMs with these signaling pathways relevant for CRC development is an important prerequisite for the validation of TRIM proteins as novel biomarkers and as potential targets of future therapies for CRC.
Highlights
Colorectal cancer (CRC) currently represents the third most prevailing cancer and a leading cause of all human cancer deaths worldwide [1,2]
We summarized recent advances in deciphering the diverse roles of tripartite motif (TRIM) proteins in CRC development and progression
An increasing number of studies has documented that TRIM proteins are being abundantly expressed in tissues from patients with CRC when compared to matched non-cancerous tissues
Summary
Colorectal cancer (CRC) currently represents the third most prevailing cancer and a leading cause of all human cancer deaths worldwide [1,2]. The ubiquitin system is not exclusively relevant for degradation of proteins, but is involved in the regulation of protein–protein interactions and many diverse intracellular processes—e.g., receptor internalization, intracellular trafficking, regulation of signaling modules, modulation of transcription factors, and chromatin modification [21]. The activation of these distinct cellular features is achieved through diverse lysine (K)-specific ubiquitination. For an in-depth overview of the significance and therapeutic implication of the other RING-type E3 ligases in colorectal cancer we refer to a review by our colleagues [18]
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