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


METHODS
The 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.


RESULTS
In 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.


CONCLUSIONS
All 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.
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 1001 University Road, Hsinchu, Taiwan, 300, ROC. malvinjefri@hotmail.com.|Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan. malvinjefri@hotmail.com.
Malvin
M
Jefri
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 1001 University Road, Hsinchu, Taiwan, 300, ROC. y16216@hotmail.com.
Yi-Ning
YN
Huang
Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan. Wjhuang0@yahoo.com.tw.|Department of Thoracic Surgery, Mackay Memorial Hospital, Taipei, Taiwan. Wjhuang0@yahoo.com.tw.
Wen-Chien
WC
Huang
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 1001 University Road, Hsinchu, Taiwan, 300, ROC. chungsan0017019@gmail.com.
Chun-San
CS
Tai
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 1001 University Road, Hsinchu, Taiwan, 300, ROC. wenurea@yahoo.com.tw.
Wen-Liang
WL
Chen
D054392:Adipokines / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D000071451:Chitinase-3-Like Protein 1; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D011379:Prognosis
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins