Knockdown of SIPA1L3 Inhibits the Proliferation and Invasion of Non–Small Cell Lung Cancer Cells Through the Hippo Pathway

Abstract Background: SIPA1L3 is a member of the signal-induced proliferation-associated (SIPA) protein family, only limited data about the SIPA1L3 are currently available in human carcinoma. Our present study provides the expression pattern and function of SIPA1L3 in non-small cell lung cancer (NSCLC).Methods: We performed immunohistochemistry to detect the distribution of SIPA1L3 in NSCLC specimens and analyzed the relationship between SIPA1L3 expression and patients clinicopathological feature. We used small interfering RNA (siRNA) to specifically silence SIPA1L3, then investigated its effect on cell growth and invasion in human lung cancer cell lines. Western blot and immunoprecipitation were performed to show the interaction of SIPA1L3 with the core proteins of Hippo pathway, and the Hippo pathway activity.Results: Immunohistochemical staining showed that SIPA1L3 was cytoplasmic increasing in 147 of 217 cases. High levels of SIPA1L3 expression were associated with poor differentiation and a high tumor node metastasis stage, positive lymph nodal status, and poor prognosis. Downregulation of SIPA1L3 inhibited cell EMT, growth, and invasion. As well as SIPA1L3 inhibited Hippo pathway. SIPA1L3 interacted with AMOT, which inhibited AMOT binding to Pals, then decreased nuclear location of YAP.Conclusions: SIPA1L3 overexpression may be a marker for advanced NSCLC. SIPA1L3 reduction inhibits the proliferative and invasive ability of the lung cancer cells, which involves the Hippo pathway by contacting with AMOT.