Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer

Abstract

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.

Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation

“…The claudin‐1 gene promoter contains TCF/LEF‐binding sites, and decreased claudin‐1 expression has been reported after downregulation of β‐catenin. Furthermore, increased claudin‐1 expression is associated with enhanced cellular proliferation . The TF FOXO4 is involved in oxidative stress and insulin signaling, longevity, cell cycle progression, and apoptosis.…”

“…Furthermore, increased claudin-1 expression is associated with enhanced cellular proliferation. 91 The TF FOXO4 is involved in oxidative stress and insulin signaling, longevity, cell cycle progression, and apoptosis. Downregulation of claudin-1 was noted in epithelial cells after FOXO4 depletion.…”

Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment

“…Another identified miR-29a target CLDN1 is a tight junction protein that facilitates cell-ECM communication and EMT in various cancer types [54][55][56]. The gene is shown to be a contributor in tumor-stroma crosstalk in pancreatic cancer [57].…”

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

“…Abnormal expression and distribution of claudin proteins may disrupt the structure and function of tight junctions, leading to damage of the gastric mucosal barrier and thereby allowing abnormal lateral diffusion of intracellular molecules and the invasion of bacteria and virulence factors from gastric mucosa into the organic body, which may result in the occurrence of many kinds of gastric diseases and even gastric cancer [4]. For example, claudin-1, which is highly expressed in the intestinal type of gastric cancer, is correlated with tumor invasion and migration and poor prognosis and overexpression of claudin-1 may promote the proliferation and migration of gastric cancer cells [5–7]. Downregulation of claudin-18 has been shown to be related to proliferation and migration of gastric cancer cells [8].…”