SPOCK2 Expression Correlates with Non-Small Cell Lung Cancer Proliferation, Invasion, and Tumorigenesis

Abstract Purpose: Lung cancer is one of the leading causes of death worldwide. Sparc (osteonectin), cwcv, and Kazal-like domains proteoglycan 2 (SPOCK2) play important roles in the development and progression of various types of human cancers. However, the role of SPOCK2 in non-small-cell lung cancer (NSCLC) is unclear. Hence, we aimed to elucidate the role of SPOCK2 in NSCLC. Methods: Real-time PCR and immunohistochemistry were used to study the relationship between SPOCK2 expression and the clinicopathology of NSCLC. SPOCK2 expression was modulated using siRNA (knockdown) or pcmv6-myc-DDK-SPOCK2 (overexpression). The invasion and migration abilities of NSCLC cells were assessed using a Transwell chamber assay, and cell proliferation was studied using the MTT and colony formation assays. Furthermore, axilla and tail vein inoculation using nude mice helped elucidate the function of SPOCK2 in vivo. The expression of related proteins was analyzed using western blotting. SPOCK2 methylation was detected using real-time PCR following the treatment of cells with decitabine. Results: The mRNA and protein levels of SPOCK2 were lower in NSCLC tissues than in adjacent normal lung tissues. SPOCK2 overexpression inhibited cell proliferation, migration, and invasion in A549, H1299 cells, and nude mice. Notch and Erk signaling pathways were inhibited by SPOCK2, whereas the Hippo pathway was activated. SPOCK2 was methylated in NSCLC cell lines. SPOCK2 expression was negatively correlated with NSCLC progression. Conclusion: Taken together, our findings indicate that SPOCK2 methylation may result in its low expression, and the levels of SPOCK2 methylation may be associated with poor prognosis in NSCLC.