Colorectal cancer (CRC) is among the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for the development of new therapeutic approaches for the treatment of CRC. Accumulating evidence has revealed that niclosamide, an anthelminthic drug, exerts antitumor activity in several types of cancer, including colon cancer. However, the underlying molecular mechanisms responsible for the effects of this drug remain elusive. Previous studies have shown that the aberrant Notch signaling pathway contributes to the carcinogenesis of colon cancer. Herein, we examined the effects of niclosamide on the growth, migration and apoptosis of colon cancer cells, and the role of the Notch signaling pathway. By performing MTT, wound-healing and Transwell migration assays, we observed that niclosamide suppressed the growth and migration of colon cancer cells, and flow cytometry demonstrated that cell apoptosis was induced. This was associated with the decreased protein expression of Notch1, Notch2, Notch3 and Hey1, and the increased expression of the tumor suppressor microRNA (miR or miRNA)-200 family members (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) that are typically downregulated in colon cancer. Collectively, these findings demonstrate that niclosamide potentially inhibits the progression of colon cancer by downregulating Notch signaling and by upregulating the miR-200 family members.

BackgroundTumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process.MethodsColon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined.ResultsIn our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis.ConclusionsThese results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0383-x) contains supplementary material, which is available to authorized users.

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0639-2) contains supplementary material, which is available to authorized users.

DC-SIGN is previously focused on its physiologic and pathophysiologic roles in immune cells. Little is known about whether DC-SIGN is expressed in malignant epithelial cells and how DC-SIGN participates in tumor progression. Here we showed that DC-SIGN expression was increased in metastatic colorectal cancer (CRC) cell lines and patient tissues. The overall survival in CRC patients with positive DC-SIGN was remarkably reduced. Gain of DC-SIGN function facilitated the CRC metastases both in vitro and in vivo, and this effect was reversed by miR-185. DC-SIGN and Lyn interacted physically, and Lyn maintained the stability of DC-SIGN in cells. DC-SIGN activation recruited Lyn and p85 to form the DC-SIGN-Lyn-p85 complex, which promoted CRC metastasis by increasing PI3K/Akt/β-catenin signaling in tyrosine kinase Lyndependent manner. Furthermore, activation of DC-SIGN promoted the transcription of MMP-9 and VEGF by increasing PI3K/Akt/β-catenin signaling, and induced TCF1/LEF1-mediated suppression of miR-185. Our findings reveal the presence of the DC-SIGN-TCF1/LEF1-miR-185 loop in cancer cells with metastatic traits, implying that it may represent a new pathogenic mechanism of CRC metastasis. This character of the loop promises to provide new targets for blocking CRC invasive and metastatic activity.

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