YKL-40 regulated epithelial-mesenchymal transition and migration/invasion enhancement in non-small cell lung cancer

Abstract

BackgroundYKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. However, the function of this protein is still unclear.MethodsThe clinical prognosis of non-small cell lung cancers (NSCLC) patients and their clinical YKL-40 expressions were obtained from the Prognoscan database. The expressions of YKL-40 in patient samples were determined by Western Blotting assay. YKL-40 gene knockdown and overexpression were performed on NSCLC cancer cells (CL1-1 and CL1-5). The cells were investigated for their epithelial–mesenchymal transition (EMT) markers gene modulation through Western Blotting and RT-PCR. Further cell metastatic abilities were assessed by transwell migration and invasion assay.ResultIn this study, YKL-40 was observed to be highly expressed in NSCLC specimens. Furthermore, determined by the PrognoScan database analysis, patients with high expression levels of YKL-40 were found with poor prognosis. In the in vitro study, different characteristics of NSCLC cell lines (CL1-1, H23, H838, CL1-5, and H2009) were used as study models, where YKL-40 expression levels were determined to correlate with the phenotypic characteristics of cancer metastasis. In this study,YKL-40 was demonstrated to regulate EMT marker expressions such as Twist, Snail, Slug, N-cadherin, Vimentin, and E-cadherin. The protein’s affects in cancer cell migration and invasion were also observed in YKL-40 overexpression or knock down NSCLC cell lines.ConclusionAll of results from this study suggest that YKL-40 is a major factor in NSCLC metastasis. Thus, YKL-40 may serve as therapeutic targets for NSCLC patients in the future.

Prognostic and Clinicopathological Value of the Expression of FOXC2 & YKL-40 in Carcinoma of the Breast, an Immunohistochemical Study

“…Additionally, Shao et al [25], have identified that the YKL-40 expression levels are associated with breast cancer vascular invasion. Jefri et al [27], assessed YKL-40 gene expression in lung cancer and found similar association between gene expression and patients' prognosis of lung cancer.…”

“…Hence, YKL-40 could to be used as a novel prognostic factor for expecting out come of carcinoma patients, more over it could be a promising targeted therapy [34]. Jefri et al [27] & Hao et al [28], proved the role of YKL-40 in EMT induc- kinase (PI3K)/AKT/mTOR cascade, which is connected with tumor survival, invasion, and metastasis and is a central feature of EMT [28].…”

Effects of a Small Interfering RNA Targeting YKL-40 Gene on the Proliferation and Invasion of Endometrial Cancer HEC-1A Cells

“…21 YKL-40 overexpression might also be associated with non-small cell lung cancer CL1-1, CL1-5 cells (NSCLC). 24 Studies have explored the inhibitory effects of YKL-40 on tumor growth and angiogenesis induced by YKL-40 in vivo. In astrocytoma, YKL-40 has been shown to induce angiogenesis and metastasis.…”

Chitinase-Like Proteins as Promising Markers in Cancer Patients

“…In YKL-40 overexpressed cell line, the expression of E-cadherin, a marker of epithelial cells, was significantly lower; and the expression of markers of mesenchymal cells (N-cadherin, Vimentin) was significantly higher as well as other EMT regulators (Snail, Slug, and Twist) [35]. Moreover, inhibition of YKL-40 reduced the tube formation in vitro and suppressed tumor growth, angiogenesis, and progression of brain tumors [28].…”