Abstract PS16-32: Obg-like ATPase 1 enhances chemoresistance of breast cancer via activation of TGF-β/Smad axis cascades

Abstract

Abstract Background: Understanding the molecular mechanism of drug resistance helps identify aneffective target for therapy of breast cancer. We investigated in this study the regulatory role ofObg-like ATPase 1 playing in multiple drug resistance of breast cancer.Methods: Paclitaxel resistant cell line (MCF-7-PTR) was developed by a continuous increasingpaclitaxel concentration. MTT assay was used to validate either acquired resistant or OLA1modified cell lines. qRT-PCR, immunoblot, apoptosis and cell cycle assays were performed toassess expression of genes and proteins in cell lines. A series of in vitro assays was performed inthe cells with RNAi-mediated knockdown to elucidate the regulatory role of OLA1 in breast cancer.Findings: We demonstrated that OLA1 was highly correlated with either acquired or intrinsicresistance of breast cancer. Further study showed that escalated expression of OLA1 promotedEMT process in tumor cells through TGF-β/Smad signaling cascades, resulting in the enhancedexpression of anti-apoptosis-related proteins (cleaved caspase3, Bax, Bcl-2) and the strengthendepolymerization of microtubules in tumor cells. Our findings revealed that OLA1 enhanced theanti-apoptotic ability and elucidated a regulatory role of OLA1 in promoting drug resistance ofbreast cancer.Interpretation: OLA1 is highly correlated with drug resistance of breast cancer. Chemo-sensitivity of the disease can be thus enhanced significantly by knocked down OLA1,which ledto inactivation of the TGF-β/Smad signaling cascades, polymerized microtubules, and promotedcell apoptosis. Our data suggest that OLA1 may be developed as a potential target to improvechemotherapy of patients with breast cancer.Keywords: breast cancer; Obg-like ATPase 1; multidrug resistance; γ-tubulin; paclitaxel Citation Format: Gary Xiao, Jianzhou Liu, Xiaoyu Miao. Obg-like ATPase 1 enhances chemoresistance of breast cancer via activation of TGF-β/Smad axis cascades [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-32.