CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway

Abstract

CAMSAP2 has been reported to act as an oncogene in hepatocellular carcinoma. However, the expression CAMSAP2 and its potential roles in colorectal cancer remain unclear. In this study, qRT-PCR and immunoblotting analysis were used to detect the mRNA and protein levels of CAMSAP2 in colorectal cancer tissues and cell lines. Wound-healing, transwell migration and invasion assay were performed to determine whether CAMSAP2 promotes the capabilities of migration and invasion of colorectal cancer cells. The results showed that CAMSAP2 was highly elevated in colorectal cancer tissues and cell lines. Moreover, the high CAMSAP2 expression was positively correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and the poor prognosis of colorectal cancer. Additionally, ectopic expression of CAMSAP2 in colorectal cancer cells promoted the migration and invasion in vitro and enhanced the lung metastasis in nude mice. Conversely, silencing CAMSAP2 resulted in an opposite phenomenon. By gain- and loss-of function experiments, we demonstrated that MMP-1 was a substantial downstream target of CAMSAP2, and it played a crucial role in regulating the migration and invasion induced by CAMSAP2 in colorectal cancer cells. Mechanistically, CAMSAP2 promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated the transcription activity of MMP-1. Taken together, our findings demonstrated that CAMSAP2 promoted colorectal cancer cell migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating CAMSAP2 is a promising therapeutic target for the treatment of metastatic colorectal cancer patients.

Potential Mechanism of Tibetan Medicine Liuwei Muxiang Pills against Colorectal Cancer: Network Pharmacology and Bioinformatics Analyses

“…One of them, TUBB3, was found to have a positive correlation with epithelial–mesenchymal transition, cell growth, and apoptosis in several CRC cell lines [ 30 , 31 ]. As a crucial part of the CRC-related JNK signaling pathway, JUN can be regulated by numerous upstream targets to further impact tumor growth, CRC cell invasion, and apoptosis [ 32 , 33 ]. In accordance with the results of our KEGG analysis, Yan et al recently found that in the IL-17 pathway, the deletion of the IL-17 receptor decreases the expression level of A20, which activates the JNK/c-JUN pathway and promotes tumor invasion, growth, and metastasis in patients with CRC [ 34 ].…”

A Marine Collagen-Based 3D Scaffold for In Vitro Modeling of Human Prostate Cancer Niche and Anti-Cancer Therapeutic Discovery

“…Integrin α 2 β 1 regulates self-renewal in prostate CSCs by interacting with ECM proteins, particularly collagen, to maintain the stem cell niche and support CSC self-renewal, facilitating tumor initiation by CSCs [91]. Integrin α 3 β 1 interaction with laminin activates signaling pathways, promotes CSC proliferation, and drives tumor growth and progression, thereby facilitating effective interaction of prostate CSCs with the tumor microenvironment, which is crucial for maintaining the stem cell niche and ensuring CSC maintenance and protection [95]. Integrin α 5 β 1 binds primarily to fibronectin, which is crucial for cell adhesion, migration, and survival.…”

The epithelial adherens junction component PLEKHA7 regulates ECM remodeling and cell behavior through miRNA-mediated regulation of MMP1 and LOX

“…These observations indicate that PLEKHA7 regulates LOX through miR-30c and MMP1 through miR-24 or miR-30c not directly, but through intermediate targets. One such intermediate target could be the JUN (cellular homolog of Jun avian sarcoma virus 17 proto-oncogene), which is responsible for MMP1 and LOX mRNA transcription (46)(47)(48)(49) and that we have previously shown to be suppressed by PLEKHA7 through miR-24 (10,11). Additional studies have also shown that miR-30 miRNAs suppress JUN (50).…”