Abnormal spindle-like microcephaly-associated protein enhances cell invasion through Wnt/β-catenin-dependent regulation of epithelial-mesenchymal transition in non-small cell lung cancer cells

Lung cancer is one of the most common cancer worldwide, invasion and metastasis are still the bottleneck in the clinical setting. More diagnostic markers and drug targets need to be clarified. Therefore, we screened abnormal spindle-like microcephaly-associated protein (ASPM) as our candidate gene, which is associated with the poor prognosis. The

ASPM promoted NSCLC invasion through EMT and by affecting the MMP family of proteins. The Wnt/β-catenin signaling pathway played an indispensable role in the ASPM-mediated NSCLC EMT-invasion cascade.

Gene Expression Omnibus (GEO) datamining was used to identify ASPM. Transwell invasion assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to discover the molecular functions of ASPM. Overexpression and small interfering mediated knockdown techniques have been used to study the cell invasion hallmarks of cancer.

ASPM stood out among all the candidate genes from GEO datamining. ASPM in lung cancer tissues has been associated with poor overall survival rate. The protein levels of ASPM has been validated using lung cancer patients' tissues, which upregulation of ASPM expression has been found in lung cancer patients. Silencing of ASPM decreased the cell invasion reflected by epithelial-mesenchymal transition (EMT) biomarkers: downregulation of vimentin and upregulation of E-cadherin. Matrix metalloproteinase (MMP) 2/9 protein levels were also affected upon transient knockdown of ASPM. Furthermore, the suppression of ASPM markedly inhibited the Wnt/β-catenin signaling pathway in vitro. The ectopic expression of ASPM had the opposite effect. The inhibition of β-catenin in ASPM-overexpressing lung cancer cells reduced the expression of EMT markers. The inhibitory effects on the Wnt/β-catenin signaling pathway were attenuated in cancer cells when ASPM was silenced. These findings demonstrated that the silencing of ASPM strongly reduced cell invasion in lung cancer. Conclusions: ASPM promoted NSCLC invasion through EMT and by affecting the MMP family of proteins. The Wnt/β-catenin signaling pathway played an indispensable role in the ASPM-mediated NSCLC EMT-invasion cascade.