HMMR promotes peritoneal implantation of gastric cancer by increasing cell–cell interactions

Abstract

Abstract Background Distant metastasis is the prominent factor for cancer-induced death of gastric cancer in which peritoneum is one of the dominating targets of gastric cancer metastasis. However, there is still a lack of effective predictive indicators and treatment methods for gastric cancer patients with peritoneal metastasis. Methods A clustering assay was used to investigate the cell aggregates formation ability. While the soft agar assay and anoikis assay were performed to detect the anchorage-independent growth and anoikis-resistant ability respectively. Luciferase activity assay, western blotting and immunofluorescence were used to explore the effect of HMMR on AKT signaling activity. The peritoneal implantation model was examined to explore the role of HMMR in vivo. Results Silencing of HMMR expression markedly reduced the peritoneal metastasis of gastric cancer cells through reducing cell–cell interactions. Mechanistically, HA-HMMR could activate Akt signaling, thus succeeding in distant colonization and metastatic outgrowth. Importantly, inducible depletion of HMMR significantly abrogates peritoneal implantation of gastric cancer in vitro and in vivo. Conclusion Our study highlights that HMMR promotes peritoneal implantation of gastric cancer. A better understanding of HMMR’s functions and mechanism might provide a novel therapeutic target and prognostic marker for metastatic gastric cancer.

Keywords

• Gastric cancer
• HMMR
• HA
• Metastasis
• Cell–cell interaction