TRIM29: A New Target in Treatment of Squamous Cell Carcinoma?

The tripartite motif-containing protein 29 (TRIM29)–keratin axis could become a potential new drug target in the treatment of squamous cell carcinoma (SCC), according to a recent study published in Cancer Research.

“Our findings reveal a critical function of TRIM29 in regulating keratin distribution as well as migration/invasion of SCC,” wrote the authors, led by Teruki Yanagi, MD, PhD, a faculty member in the Department of Dermatology at Hokkaido University in Japan.

TRIM family proteins function in various ways during cellular processes, including intracellular signaling, cell development, protein quality control, apoptosis, and carcinogenesis. A member of the TRIM family of proteins, TRIM29 has been linked to breast, colorectal, and pancreatic cancers.

A recent survey of TRIM29 in a range of cancers suggested that upregulated TRIM29 expression predicted poor prognosis in patients with malignant neoplasms. However, its role in SCC is currently unknown. Searches of public databases revealed that TRIM29 is highly expressed in stratified epithelial tissues found at the level of the head and neck.

In the current study, Yanagi et al analyzed TRIM29 expression in cutaneous head and neck squamous cell carcinomas (SCC), as well as its tumorigenic roles.

The researchers observed that TRIM29 expression was lower in malignant SCC lesions compared with adjacent normal epithelial tissue or benign tumors. This decreased TRIM29 expression correlated with higher SCC invasiveness.

Primary tumors of cutaneous SCC demonstrated aberrant hypermethylation of the CpG lesion of TRIM29. In a related finding, TRIM29 expression in these tumors was also associated with the altered keratin expression and distribution. The team also found that depleting TRIM29 heightened the migration of cancer cells, whereas TRIM29 overexpression subdued this migration.

Utilizing non-biased comprehensive proteomics and immunoprecipitation analyses, Yanagi et al identified keratins and the keratin-interacting protein FAM83H as TRIM29 interactors. Finally, the investigators discovered that the RNAi-mediated gene-knockdown of TRIM29 led to ectopic keratin localization of keratinocytes.

“We revealed an unrecognized role of TRIM29 in the cell migration/invasion of cutaneous and head/neck SCC tumors,” the authors concluded. “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.”

In an interview with Cancer Network, dermatologist Jerry D. Brewer, MD, MS, a dermatologist and professor of dermatology at the Mayo Clinic, considered the potential implications of the study. “This is an interesting study, the findings of which may spur further research or even drive treatment strategies in the future for cutaneous SCC.”