High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients. Issue 2 (1st May 2016)

• Record Type: Journal Article
• Authors: Kim, Patrick Y.; Tan, Owen; Liu, Bing; Trahair, Toby; Liu, Tao; Haber, Michelle; Norris, Murray D.; Marshall, Glenn M.; Cheung, Belamy B.
• Is Part Of: Cancer letters. Volume 374:Issue 2(2016)
• Page Start: 315
• Page End: 323
• Publication Date: 2016-05-01
• Subjects: TRIM16 -- TDP43 -- Neuroblastoma -- Breast cancer -- Yeast two-hybrid assay; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.02.021
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: TRIM16 interacts and regulates TDP43 protein levels. TDP43 is required for TRIM16 induced cancer cell death. TRIM16 and TDP43 together modulate pRb and E2F1 proteins. TRIM16 and TDP43 are strong prognostic indicators for neuroblastoma and breast cancer. Abstract: Tripartite Motif-containing protein 16 (TRIM16) is a member of a large family of tripartite motif (TRIM) proteins, that has been implicated in the pathogenesis of multiple cancers. However, the mechanism by which TRIM16 acts as a tumour suppressor is currently unknown. We used the versatile yeast two-hybrid assay on a cDNA library from human testes, which has relative high TRIM16 expression, to identify potential TRIM16-binding proteins. We identified transactive response DNA-binding protein 43 (TDP43) as a novel TRIM16 binding protein. Co-immunoprecipitation assay demonstrated that TDP43 bound TRIM16 in neuroblastoma and breast cancer cells. Enforced over-expression of TRIM16 increased the protein half-life of TDP43, through the inhibition of the proteosomal degradation pathway. High levels of TRIM16 and TDP43 are associated with good prognosis in both human neuroblastoma and breast cancer tissues. Importantly, we found TDP43 expression was required for TRIM16-induced inhibition of neuroblastoma and breast cancer cell growth and the repressive effect of TRIM16 on cell cycle regulatory proteins, E2F1 and pRb. Taken together, our data suggest that TRIM16 and TDP43 are both good prognosis indicators; also we showed that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins.