H Wan1, Z Li1, H Wang2, F Cai3, L Wang4. 1. Department of Oncology, Sanya People's Hospital, Sanya, 572000, China. 2. Department of Pathology, Sanya People's Hospital, Sanya, 572000, China. 3. Department of Pharmacy, Sanya People's Hospital, Sanya, 572000, China. 4. Department of Oncology, Hainan General Hospital, No.19, Xinhua Road, Xiuying District, Haikou, 570311, Hainan, China. wanglin7209@163.com.
Abstract
BACKGROUND: Chemoresistance is the major cause of therapeutic failure in triple negative breast cancer (TNBC). In this work, we investigated the molecular mechanism for the development of TNBC chemoresistance. METHODS: mRNA and protein levels of ST8SIA1 were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation and survival assays were performed to determine the role of ST8SIA1 in TNBC chemoresistance. RESULTS: We found that ST8SIA1 mRNA and protein levels were increased in multiple TNBC cell lines after prolonged exposure to chemotherapeutic drugs. Consistently, retrospective study demonstrated that the majority of TNBC patients who developed chemoresistance displayed upregulation of ST8SIA1. We further found that chemoresistant TNBC cells were more sensitive than chemosensitive cells to ST8SIA1 inhibition in decreasing growth and viability. Consistently, ST8SIA1 inhibition augmented the efficacy of chemotherapy in TNBC cells. Mechanism studies demonstrated that ST8SIA1 inhibition led to suppression of FAK/Akt/mTOR and Wnt/β-catenin signalling pathways. CONCLUSIONS: These findings provide an explanation for the heterogeneity of chemotherapy responses across TNBC individuals and reveal the supportive roles of ST8SIA1in TNBC chemoresistance.
BACKGROUND: Chemoresistance is the major cause of therapeutic failure in triple negative breast cancer (TNBC). In this work, we investigated the molecular mechanism for the development of TNBC chemoresistance. METHODS: mRNA and protein levels of ST8SIA1 were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation and survival assays were performed to determine the role of ST8SIA1 in TNBC chemoresistance. RESULTS: We found that ST8SIA1 mRNA and protein levels were increased in multiple TNBC cell lines after prolonged exposure to chemotherapeutic drugs. Consistently, retrospective study demonstrated that the majority of TNBC patients who developed chemoresistance displayed upregulation of ST8SIA1. We further found that chemoresistant TNBC cells were more sensitive than chemosensitive cells to ST8SIA1 inhibition in decreasing growth and viability. Consistently, ST8SIA1 inhibition augmented the efficacy of chemotherapy in TNBC cells. Mechanism studies demonstrated that ST8SIA1 inhibition led to suppression of FAK/Akt/mTOR and Wnt/β-catenin signalling pathways. CONCLUSIONS: These findings provide an explanation for the heterogeneity of chemotherapy responses across TNBC individuals and reveal the supportive roles of ST8SIA1in TNBC chemoresistance.
Authors: Ancy Thomas; Saurav Sumughan; Emilia R Dellacecca; Rohan S Shivde; Nicola Lancki; Zhussipbek Mukhatayev; Cristina C Vaca; Fei Han; Levi Barse; Steven W Henning; Jesus Zamora-Pineda; Suhail Akhtar; Nikhilesh Gupta; Jasmine O Zahid; Stephanie R Zack; Prathyaya Ramesh; Dinesh Jaishankar; Agnes Sy Lo; Joel Moss; Maria M Picken; Thomas N Darling; Denise M Scholtens; Daniel F Dilling; Richard P Junghans; I Caroline Le Poole Journal: JCI Insight Date: 2021-11-22
Authors: Lei Wang; Wuxiyar Otkur; Aman Wang; Wen Wang; Yitong Lyu; Lei Fang; Xiu Shan; Mingzhou Song; Yan Feng; Yi Zhao; Hai-Long Piao; Huan Qi; Ji-Wei Liu Journal: Front Pharmacol Date: 2022-08-12 Impact factor: 5.988