Abstract
BackgroundProfiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis. However, DC-SIGNR as a family member of selectin participates in gastric cancer liver metastasis remains unknown.MethodsThe serum level of DC-SIGNR was evaluated in gastric cancer patients by ELISA. Manipulation DC-SIGNR expression in BGC823 and SGC7901 cell lines was mediated by lentivirus. Investigation the biological effects of DC-SIGNR were verified by MTT, wounding and transwell in vitro and experiments on animals to confirm gastric cancer liver metastasis by IVIS. Insights of the mechanism were employed microarray and bioinformatic analysis. Further to confirm the results were conducted by qRT-PCR, western blot and by flow cytometry.ResultsDC-SIGNR serum level was significantly increased in gastric cancer patients compared with healthy group. Additionally, DC-SIGNR level was associated with an advanced pathological stage in gastric cancer patients. DC-SIGNR knockdown inhibited the proliferation, migration and invasion of gastric cancer cells in vitro and suppressed the liver metastasis in vivo. While, DC-SIGNR overexpression promoted cell proliferation, migration and invasion. In mechanism, HNRNPKP2 as a lncRNA was upregulated after DC-SIGNR knockdown. Importantly, STAT5A promoted HNRNPKP2 expression after knockdown DC-SIGNR. Furthermore after HNRNPKP2 depletion, the downstream target gene CXCR4 was downregulated.ConclusionsDC-SIGNR promoted gastric cancer liver metastasis mediated with HNRNPKP2 which expression was regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target gene CXCR4. These findings indicated potential therapeutic candidates for gastric cancer liver metastasis.
Highlights
Profiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis
DC-SIGNR is increased in gastric cancer serum and correlates with advanced pathological stage ELISA analysis was used to examine the DC-SIGNR level in 207 gastric cancer serum and 197 healthy group
DC-SIGNR was significantly increased in gastric cancer patients with liver metastasis compared with patients with no metastasis (Fig. 1c)
Summary
Profiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis. DC-SIGNR as a family member of selectin participates in gastric cancer liver metastasis remains unknown. Researchers demonstrate that liver sinusoidal endothelial cell lectin (LSECtin) mediated colon cancer cells metastasis to liver displays enhanced abilities to the specific organ [8]. Hepatic sinusoidal endothelial E-selectin expression is up regulated by highly metastatic cells entering the liver [10]. Using an E-selectin-specific monoclonal antibody reduces liver metastasis, showing that Eselectin is involved in metastatic formation in this organ [11]. For further study, blocking colorectal carcinomainduced hepatic endothelial E-selectin expression inhibits liver metastasis [12]. These events suggest that selectin play a key role in tumour metastasis to the target organs. We ask whether DC-SIGNR contributes to hematogenous metastasis from gastric carcinoma
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