Kholoud Arafat1, Elham Al Kubaisy1, Shahrazad Sulaiman1, Sherif M Karam2, Zeina Al Natour3, Ahmed H Hassan3,4, Samir Attoub1,5. 1. Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. 2. Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. 3. Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. 4. Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, United Arab Emirates. 5. Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
Abstract
BACKGROUND/AIMS: Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-negative breast cancers have the worst prognosis. The identification of new genes associated with triple-negative breast cancer progression is crucial for developing more specific anti-cancer targeted therapies, which could lead to a better management of these patients. In this context, we have recently demonstrated that SMARCAD1, a DEAD/H box-containing helicase, is involved in breast cancer cell migration, invasion, and metastasis. The aim of this study was to investigate the impact of the stable knockdown of SMARCAD1 on human breast cancer cell progression. METHODS: Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of the stable knockdown of SMARCAD1 on human breast cancer cell proliferation and colony growth in vitro and on tumour growth in chick embryo and nude mouse xenograft models in vivo using MDA-MB-231 (ER-/PR-/ HER2-) and T47D (ER+/PR+/-/HER2-) human breast cancer cell lines. RESULTS: We found that SMARCAD1 knockdown resulted in a significant decrease in breast cancer cell proliferation and colony formation, leading to the significant inhibition of tumour growth in both the chick embryo and nude mouse xenograft models. This inhibition was due, at least in part, to a decrease in IKKβ expression. CONCLUSION: These results indicate that SMARCAD1 is involved in breast cancer progression and can be a promising target for breast cancer therapy.
BACKGROUND/AIMS: Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-negative breast cancers have the worst prognosis. The identification of new genes associated with triple-negative breast cancer progression is crucial for developing more specific anti-cancer targeted therapies, which could lead to a better management of these patients. In this context, we have recently demonstrated that SMARCAD1, a DEAD/H box-containing helicase, is involved in breast cancer cell migration, invasion, and metastasis. The aim of this study was to investigate the impact of the stable knockdown of SMARCAD1 on humanbreast cancer cell progression. METHODS: Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of the stable knockdown of SMARCAD1 on humanbreast cancer cell proliferation and colony growth in vitro and on tumour growth in chick embryo and nude mouse xenograft models in vivo using MDA-MB-231 (ER-/PR-/ HER2-) and T47D (ER+/PR+/-/HER2-) humanbreast cancer cell lines. RESULTS: We found that SMARCAD1 knockdown resulted in a significant decrease in breast cancer cell proliferation and colony formation, leading to the significant inhibition of tumour growth in both the chick embryo and nude mouse xenograft models. This inhibition was due, at least in part, to a decrease in IKKβ expression. CONCLUSION: These results indicate that SMARCAD1 is involved in breast cancer progression and can be a promising target for breast cancer therapy.
Authors: Calvin Shun Yu Lo; Marvin van Toorn; Vincent Gaggioli; Mariana Paes Dias; Yifan Zhu; Eleni Maria Manolika; Wei Zhao; Marit van der Does; Chirantani Mukherjee; João G S C Souto Gonçalves; Martin E van Royen; Pim J French; Jeroen Demmers; Ihor Smal; Hannes Lans; David Wheeler; Jos Jonkers; Arnab Ray Chaudhuri; Jurgen A Marteijn; Nitika Taneja Journal: Sci Adv Date: 2021-05-05 Impact factor: 14.136