Abstract
BackgroundOur previous screening study suggested that the cell-adhesions protein Dihydropyrimidinase-like 3 (DPYSL3) was a candidate metastatic lung cancer related molecule. This study aimed to analyze the correlation between DPYSL3 and metastatic lung cancer.MethodsStable DPYSL3 knockdown Lewis lung carcinoma (LLC) cells were constructed with a retroviral system. Cell migration and invasion assays were performed to determine the role of DPYSL3 in LLC cells’ migration and invasion changes. A metastatic lung tumor model in which the stable DPYSL3 knockdown LLC cells were injected through tail vein was used to analyze the role of DPYSL3 in tumor metastasis in vivo. The correlation between DPYSL3 expression and the survival time of lung cancer patients were analyzed in KMPLOT database.ResultsKnockdown of DPYSL3 promoted the migratory and invasive of LLC cells compared to the control group. Meanwhile, the motility of LLC cells was also increased with the inhibition of DPYSL3. The TGFβ-induced EMT increased when DPYSL3 was inhibited. The expression of EMT markers, TWIST1 and N-cadherin, significantly increased to almost two times with the knockdown of DPYSL3. Furthermore, inhibition of DPYSL3 promoted the progression of metastatic xenograft in C57BL/6 mice. The expression level of DPYSL3 decreased in lung cancer patients with distant metastasis.ConclusionsKnockdown of DPYSL3 promoted the metastatic ability of LLC cells in vitro and in vivo.
Highlights
Our previous screening study suggested that the cell-adhesions protein Dihydropyrimidinase-like 3 (DPYSL3) was a candidate metastatic lung cancer related molecule
Knockdown of DPYSL3 promotes the motility of Lewis lung carcinoma (LLC) cells In order to further analyze the role of DPYSL3 in progression and invasion of lung cancer, we first observed the motility changes of LLC cells caused by knockdown DPYSL3
Statistical analysis All data were analyzed by the SPSS package for Windows (Version 18.0, Chicago, IL). t test was used to analyze the results of cell motility, proliferation, Fig. 2 The proliferation of LLC cells was not affected by DPYSL3
Summary
Our previous screening study suggested that the cell-adhesions protein Dihydropyrimidinase-like 3 (DPYSL3) was a candidate metastatic lung cancer related molecule. This study aimed to analyze the correlation between DPYSL3 and metastatic lung cancer. Lung cancer is the leading cause of cancer mortality around the world [1]. The advanced improvements have been made in the diagnosis and treatment, the 5-year survival rate of lung cancer patients is still far from satisfactory. Metastasis is a dynamic interaction between cancer cells and microenvironments. It was thought as a late event and only occurred when primary lesion had progressed locally. Recent evidences suggested that metastasis occurred in early-stage due to the spread of circulating tumor cells [2, 3]
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