Abstract B17: TRIM24 links epigenetics and metabolism in cancer

The TRIpartite Motif (TRIM) family of proteins has approximately 70 proteins, which are involved in a variety of processes, including regulation of protein stability, transcription, cell proliferation and apoptosis. Our laboratory discovered TRIM24, as an E3-ubiquitin ligase of p53, using embryonic stem cells and breast cancer cell lines as model systems. Earlier reports identified TRIM24 as a transcriptional co-regulator of nuclear receptor signaling, directly interacting with retinoic-acid receptor (RAR), thyroid receptor, androgen receptor and estrogen receptor (ER). Since our laboratory's initial report showing TRIM24 over expression correlates with poor survival of breast cancer patients, several studies reported roles of TRIM24 in multiple cancers such as NSLC, head and neck carcinoma, hepatocellular carcinoma, colorectal cancer and glioblastoma.We found that TRIM24 expression is deregulated during breast cancer progression and likely early in the process. I found that the ectopic expression of TRIM24 in immortalized Human mammary epithelial cells (HMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24-HMECs in nude mice displayed significantly higher xenograft volume as compared to their control counterparts. Interestingly, molecular analysis of TRIM24-HMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Using Chromati...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research