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

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

doi:10.2217/lmt-2018-0010

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

Lung Cancer Manag. 2019 Feb 26;8(1):LMT04. doi: 10.2217/lmt-2018-0010. eCollection 2019 Feb.

Authors

Lin Ma^{1

2

3

1

2

3}, Wu Yin^{3

3}, Heliang Ma^{4

4}, Ihab Elshoura^{3

3}, Lan Wang^{5

5}

Affiliations

¹ School of Materials Science & Engineering, South China University of Technology, Guangzhou 510640, China.
² R&D Center, Guangzhou Ribobio Co., Ltd, Guangzhou 510663, China.
³ State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210046, China.
⁴ Department of Radiology, Jinan Central Hospital, Jinan, Shandong 250013, China.
⁵ Department of Respiratory Medicine, The Affiliated Jiangyin Hospital of Southeast University, Jiangyin 214400, China.

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.

Keywords: CSCs; ELDA; cisplatin; claudin-3; estrogen receptor-α; nonsquamous NSCLC; side population; tight junction; tumorigenesis; cancer stemness.