Lin Ma, Wu Yin, Heliang Ma, Ihab Elshoura, Lan Wang
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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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