Targeting claudin-3 suppresses stem cell-like phenotype in nonsquamous non-small-cell lung carcinoma.

Pub Date : 2019-02-26 eCollection Date: 2019-02-01 DOI:10.2217/lmt-2018-0010
Lin Ma, Wu Yin, Heliang Ma, Ihab Elshoura, Lan Wang
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Abstract

Aim: To determine the role of claudin-3 in cancer stemness in nonsquamous non-small-cell lung carcinoma (NSCLC).

Materials & methods: In vitro/vivo extreme limiting dilution analysis and the side population assay were used to investigate the role of claudin-3 in regulating cancer stemness in nonsquamous NSCLC.

Results & conclusion: Claudin-3 depletion decreased the formation rates of spheres and tumors and increased cisplatin sensitivity. Claudin-3 was also identified as one downstream target of estrogen receptor-α in regulating cancer stemness. Moreover, targeting CLDN-3 transcription by small molecules including withaferin A, estradiol and fulvestrant suppressed cancer stemness and reversed chemoresistance. These results demonstrated claudin-3 is one positive regulator of cancer stemness in nonsuqamous NSCLC.

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靶向克劳丁-3可抑制非鳞状非小细胞肺癌的干细胞样表型。
目的:确定Claudin-3在非鳞状非小细胞肺癌(NSCLC)癌症干性中的作用:材料与方法:采用体外/体内极限稀释分析和侧群试验研究Claudin-3在非鳞状非小细胞肺癌中调控癌症干性的作用:结果与结论:Claudin-3耗竭降低了球体和肿瘤的形成率,增加了顺铂的敏感性。Claudin-3也被确定为雌激素受体-α调控癌症干性的下游靶点之一。此外,以CLDN-3转录为靶点的小分子药物,包括雌激素受体α(withaferin A)、雌二醇(estradiol)和氟维司群(fulvestrant),可抑制癌症干性并逆转化疗耐药性。这些结果表明,claudin-3是非鳞状NSCLC癌症干性的一个积极调节因子。
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