High expression of fibronectin is associated with poor prognosis, cell proliferation and malignancy via the NF-κB/p53-apoptosis signaling pathway in colorectal cancer

Abstract

Fibronectin is a glycoprotein of the extracellular matrix, and regulates the processes of self-renewal and cell cycle progression. This study aimed to investigate fibronectin expression in colorectal cancer (CRC) and elucidate the effects of fibronectin on CRC by using a knockdown approach. Immunohistochemistry was used to evaluate the expression of fibronectin in 107 CRC patient tissues and gene expression was detected by real-time quantitative PCR (qPCR) and western blot analysis. Based on the above findings, the association among fibronectin expression, clinicopathological features and prognosis was analyzed. Next, fibronectin expression was silenced by small-interfering RNAs (siRNAs) and the effects of fibronectin siRNA transfection on CRC cells and tumor growth in nude mice were assessed. Expression of genes in the NF-κB/p53-apoptosis signaling pathway were analyzed after fibronectin siRNA transfection both in vitro and in vivo. Based on the results, high expression of fibronectin was observed both in the CRC tissues and CRC cell lines. The expression level was positively correlated with TNM stage (P=0.0025) and distant metastasis (P=0.0013). By Kaplan-Meier analysis, the patients with low fibronectin expression had a longer survival time comparing to those with relatively high expression. Knockdown of fibronectin suppressed SW480 cell proliferation, migration and invasion. In addition, knockdown of fibronectin led to S phase cell cycle arrest. The following study showed that the NF-κB/p53-apoptosis signaling pathway in CRC was affected by fibronectin knockdown. Tumor formation was also depressed by fibronectin siRNA transfection of CRC cells. These results showed the significant role of fibronectin in CRC tissues and cell lines. Therefore, fibronectin may be regarded as a potential target for CRC treatment.

TCPA v3.0: An Integrative Platform to Explore the Pan-Cancer Analysis of Functional Proteomic Data

“…6C). Consistent with the previously reported patterns in breast, colorectal, and head and neck cancer types (21)(22)(23), these results suggest that fibronectin could serve as a robust prognostic marker across cancer types. As for correlations with established tumor subtypes, we found that many of the 258 protein markers were differentially expressed among the established tumor subtypes (e.g.…”

Role of the extracellular matrix in cancer‐associated epithelial to mesenchymal transition phenomenon

“…Noteworthy, specific modifications in FN structure are directly correlated to the onset of EMT. An illustrative example is that the expression of the FN splicing isoform EdB, specific for tumor tissues, is suggested to be a marker of EMT in translational oncology (Petrini et al, ; Yi et al, ).…”

Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and induces apoptosis in colorectal cancer cells

“…In CRC, NF‐κB is activated in cancer cells as well as in the surrounding microenvironment to sustain inflammation and promote proliferation, angiogenesis, invasion and eventually metastasis. Retrospective analysis indicated that activated NF‐κB is associated with tumor metastasis and poor prognosis . Thus, targeting the NF‐κB pathway has been an actively sought‐after strategy for novel anti‐CRC drug discovery, and a number of specific inhibitors have been developed for further clinical studies …”