Enhanced expression of CXCL1 in renal cell carcinoma facilitates tumor cell malignancy via PI3K/AKT-dependent mechanisms

The expression of CXC motif chemokine ligand 1 (CXCL1) is elevated in numerous types of human cancers, and CXCL1 is also able to act as an autocrine/paracrine factor to accelerate the malignant progression of malignancies. However, at present, there is limited understanding of the role of CXCL1 in renal cell carcinoma (RCC). The present study aimed to investigate the mRNA and protein expression levels of CXCL1 in RCC tissues, which were found to be markedly elevated compared with normal and paracancerous tissues using bioinformatics and immunohistochemical analyses. In addition, high expression of CXCL1 was shown to be closely associated with higher stage, grade, tumor, lymph node and metastasis status of clear cell RCC, as well as with poor prognosis in patients. In addition, the expression level of CXCL1 mRNA was found to be associated with the expression of various tumor-associated genes, including numerous chemokines and their receptors, immune cell recruitment of B cells, CD4+ T cells and neutrophils, as well as microsatellite instability in RCC. Functional studies were also performed, which demonstrated that both exogenous and overexpression of CXCL1 led to a marked enhancement of the proliferative and migratory capacities of RCC cells, whereas downregulation of CXCL1 exerted a suppressive influence on the malignant behaviors of the tumor cells. In addition, western blot analysis experiments revealed that overexpression of CXCL1 in RCC cells was able to regulate the expression levels of phosphoinositide 3-kinase (PI3K)/AKT pathway-associated proteins, including Bcl-2-associated X protein, B-cell lymphoma-2, PI3K and AKT. Finally, the AKT-specific inhibitor GDC-0068 was shown to reverse the promoting effects of CXCL1 on the malignant behaviors of RCC cells. Taken together, the findings of the present study have shown that CXCL1 exhibits high expression patterns in RCC tissues and may serve diverse functions in facilitating various aspects of RCC advancement. Keywords: CXCL1; PI3K; clinical significance; malignant behavior; renal cell carcinoma.