The Roles of HIP1 in the Metastasis of Non-Small Cell Lung Cancer (NSCLC)

Abstract

Non-small cell lung cancer (NSCLC) carries a poor survival rate mainly due to metastasis and the molecular mechanism of metastasis remains unclear Huntingtin interacting protein-1 (HIP1) is overexpressed in many human tumors but its pathological roles in the progression of lung cancer are unknown We analyzed HIP1 expressions in clinical lung specimens using immunohistochemistry (IHC) The results revealed that HIP1 expressions were very low in the normal lung tissues dramatically increased during the early tumorigenesis and decreased with NSCLC progression accompanied with metastasis We also proved that HIP1 was a NSCLC early-stage prognostic biomarker with downregulated expressions for a poor prognosis Subsequently our studies showed that HIP1 was a metastatic suppressor in NSCLC to repress significantly the mobility of lung cancer cells both in vitro and in vivo Besides we demonstrated that HIP1 repressed the epithelial-mesenchymal transition (EMT) to inhibit metastasis through blocking the AKT-GSK3β signaling axis Finally we found that HIP1 interacted with Akt to decrease its activity and proposed that HIP1 restrained Akt in the cytoplasm from its activation on the plasma membrane In conclusion HIP1 serves as an early-stage prognostic biomarker of NSCLC and a metastatic suppressor with reduced expressions during NSCLC progression to develop late metastasis and cause a poor prognosis through regulating the Akt-mediated EMT signaling pathway Our findings may put the new insight of HIP1-mediated metastasis and lead to a novel application in prognostic evaluation of NSCLC treatment

Date of Award	2015 Aug 19
Original language	English
Supervisor	Pei-Jung Lu (Supervisor)