Abstract A48: Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer

We report the identification of a truncated tumor suppressor, MAGI3, at both the mRNA and protein levels from the MDA-MB-231 breast cancer cell line. Using 3' rapid amplification of cDNA ends (RACE), we have determined that the truncated transcript arises due to premature cleavage and APA at a cryptic intronic PAS. We have previously demonstrated genetically and biochemically that MAGI3 functions as a mammary tumor suppressor by antagonizing the oncoprotein and Hippo pathway effector, YAP, via a physical sequestration mechanism. Importantly, here we find that the truncated gene product encoded by this aberrant MAGI3 transcript acts as a dominant-negative protein, preventing MAGI3-YAP physical association and thereby causing YAP nuclear activation and malignant transformation of cells. Since "epi-mutations" such as these play an important role in breast cancer development, yet cannot be detected by microarray or genome sequencing methodologies, we are currently undertaking analysis of large-scale, breast cancer RNA-Seq data to identify tumors that express the truncated driver mRNA and to determine the frequency of APA products in breast cancer. Knowledge of the clinically relevant proteins produced by APA that are unique to cancer cells may lead to new therapeutic opportunities for breast cancer.Citation Format: Thomas K. Ni, Charlotte Kuperwasser. Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer. [abstract]. In: Proceedings of the AACR ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: New Omics in Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research