Ma Sun Young, Park Jin-Hee, Jung Hana, Ha Sung-Min, Kim Yeonye, Park Dong Hyen, Lee Deuk Hee, Lee Sooyong, Chu In-Ho, Jung So Young, Kim Il-Hwan, Choi Il-Whan, Choi Chang Soo, Park Saegwang
Department of Radiation Oncology, Kosin University College of Medicine, Busan 49267, Republic of Korea.
Department of Microbiology and Immunology, INJE University College of Medicine, Busan 47392, Republic of Korea.
Oncol Rep. 2017 Sep;38(3):1867-1876. doi: 10.3892/or.2017.5834. Epub 2017 Jul 18.
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBO‑P2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials. In addition, Snail silencing also reduced resistance to chemotherapy drugs and cancer stem-like properties, such as CD44 expression, aldehyde dehydrogenase (ALDH) activity, colony formation, and in vivo tumour formation and growth. However, radioresistance was not decreased by silencing Snail. Collectively, this study suggested that Snail is a main regulator of the maintenance of malignancy potentials and is a good target to prevent cancer metastasis and to increase chemotherapy susceptibility.
Snail是一种锌指转录抑制因子,可抑制E-钙黏蛋白的表达,是上皮性癌中上皮-间质转化(EMT)的关键诱导因子之一。在乳腺癌中,EMT与恶性肿瘤相关,包括转移、癌症干细胞样特性以及对化疗和放疗的抗性。在本研究中,我们通过短发夹RNA敲低功能,分析了Snail在高转移性间充质TUBO-P2J小鼠乳腺癌细胞中的作用。虽然沉默Snail并未恢复E-钙黏蛋白的表达或诱导形态变化,但Snail沉默显著消除了体外和体内的转移潜能。此外,Snail沉默还降低了对化疗药物的抗性以及癌症干细胞样特性,如CD44表达、醛脱氢酶(ALDH)活性、集落形成以及体内肿瘤形成和生长。然而,沉默Snail并未降低放射抗性。总体而言,本研究表明Snail是维持恶性潜能的主要调节因子,是预防癌症转移和增加化疗敏感性的良好靶点。