TRIM44 family overexpression is associated with carcinogenesis, and TRIM44 has been identified as a prognostic gene. In a study reported in Journal of the National Cancer Institute, Ong and colleagues attempted to identify therapeutic strategies for patients with TRIM44 overexpression.
Genomic and transcriptomic data from 1,932 epithelial cancers, 1,980 breast cancers, and 163 esophagogastric cancers were analyzed to identify genomic alteration associated with TRIM44 overexpression. The driver gene status of TRIM44 was determined using a small interfering RNA (siRNA) screen of the 11p13 amplicon. It was found that TRIM44 overexpression resulted from genomic amplification in 16.1% of epithelial cancers, including 8.1% of esophagogastric cancers and 6.1% of breast cancers.
Computer simulation analysis showed a link between TRIM44 and mTOR signaling. Support for this link was provided by the finding of a reduction in mTOR signaling after siRNA knockdown of TRIM44 in cell lines and co-localization of TRIM44 and p-mTOR in patient samples. Studies in vitro showed that the mTOR inhibitor everolimus (Afinitor) decreased cell viability in two TRIM44-amplified cells lines by 88% and 70% compared with 35% in a control cell line. These findings were confirmed in xenograft models.
The investigators concluded, “Genomic amplification drives TRIM44 overexpression in [esophagogastric cancers and breast cancers]. Targeting the mTOR pathway provides a potential therapeutic option for TRIM44-amplified tumors.” ■
Ong C-AJ, et al: J Natl Cancer Inst. April 28, 2014 (early release online).