Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer
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Jie Huang1, Li Zhang1, Changyu He1, Ying Qu1, Jianfang Li1, Jianian Zhang1, Tao Du1, Xuehua Chen1, Yingyan Yu1, Bingya Liu1 and Zhenggang Zhu1
1 Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Bingya Liu, email:
Zhenggang Zhu, email:
Keywords: Claudin-1, Anoikis, β-catenin, Gastric cancer
Received: August 14, 2014 Accepted: December 01, 2014 Published: December 02, 2014
Claudin-1 (CLDN1) is overexpressed in gastric cancer and correlated with tumor invasion, metastasis and poor outcome. Here, we both down and up regulated CLDN1 expression in gastric cancer cells to elucidate its role in gastric carcinogenesis and tumor progression. We found that deficiency of CLDN1 inhibited cells migration, invasion, and colony formation in vitro and tumorigenicity, metastasis in vivo. Also, CLDN1 promoted cell aggregation and increased anoikis resistance. Down or up regulation of CLDN1 was accompanied with changes of membrane β-catenin expression as well as Akt and Src activities. When β-catenin was up-regulated in CLDN1-KD cells, cell aggregation and anoikis resistance were restored, and Akt and Src signal pathways were re-activated. Taken together, these findings suggest that CLDN1 is oncogenic in gastric cancer and its malignant potential may be attributed in part to regulation of anoikis, by mediating membrane β-catenin-regulated cell-cell adhesion and cell survival.
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