A recent study published in Cancer Research suggests that treatments of squamous cell carcinoma (SCC) would benefit from focusing on the tripartite motif-containing protein 29 (TRIM29)–keratin axis. The molecule has the potential to open new avenues of attack against the disease.
“We revealed an unrecognized role of TRIM29 in the cell migration/invasion of cutaneous and head/neck SCC tumors”, noted Teruki Yanagi, MD, Ph.D. of the Department of Dermatology at Hokkaido University in Japan. “The present results suggest that TRIM29 could be a novel diagnostic/prognostic marker in stratified epithelial tumors. Also, the TRIM29-keratin axis may be a novel therapeutic target in intractable/metastatic SCCs”.
The TRIM family of proteins function in various ways during cellular processes, including intracellular signaling, cell development, protein quality control, apoptosis, and carcinogenesis. Researchers linked TRIM29 to breast, colorectal, and pancreatic cancers and observed that upregulated levels predicted poor prognosis in patients with malignant neoplasms.
Malignant SCC lesions showed lower TRIM29 expressions compared to adjacent normal epithelial tissue or benign tumors. This decreased TRIM29 expression correlated with higher SCC invasiveness. In primary tumors of cutaneous SCC aberrant hypermethylation of the CpG lesion of TRIM29 were found. These were associated with the altered keratin expression and distribution. Depleting TRIM29 heightened the migration of cancer cells, whereas TRIM29 overexpression subdued this migration.
The team identified keratins and the keratin-interacting protein FAM83H as TRIM29 interactors. They determined that the RNAi-mediated gene-knockdown of TRIM29 led to ectopic keratin localization of keratinocytes.
These findings are expected to spur on further research or even drive treatment strategies in the future for cutaneous SCC.
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