Hedgehog (HH) pathway significantly affected the pathogenesis of Gastric cancer (GC), but the multiple uncanonical HH pathways that are mediated by Zinc Finger protein GLI1 (GLI1) are still unclear. In the present work, we evaluated GLI1 and p-AKT expression in GC using immunohistochemistry (IHC) analysis. GLI1 and AKT specific shRNA was transfected into GC cell lines to investigate the cross-regulation between HH pathway and AKT-mTOR pathway. The effect of GLI1 and p-AKT on proliferation, migration, and drug resistance were examined. Moreover, a mouse xenograft model of GC was established to verify the role of GLI1 and p-AKT in promoting drug sensitivity in vivo. Our results suggested the clinicopathological factors and prognosis by the differential expression of GLI1 and p-AKT in GC patients. GLI1 was activated by the AKT-mTOR pathway. Co-expression of GLI1 and p-AKT was associated with cell viability, migration, and drug resistance and indicated a poor prognosis in GC patients. Agents targeted against both GLI1 and p-AKT may reverse drug-resistance and achieve better inhibition than agents targeted against a single molecule. There was a significant correlation between the high expression of GLI1 and p-AKT in GC. Additionally, our study confirmed the activity of the AKTmTOR-GLI1 axis, which provided a new viable field for GC treatment.
[1]Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, 188 ShiZi St, Suzhou 215006, Jiangsu, Peoples R China.
[2]Soochow Univ, Affiliated Hosp 1, Dept Gastroenterol, Suzhou 215006, Jiangsu, Peoples R China.
[3]Shanghai Univ Med & Hlth Sci, Jiading Dist Cent Hosp, Dept Gen Surg, Shanghai 201800, Peoples R China.
[4]Soochow Univ, Affiliated Hosp 1, Dept Pathol, Suzhou 215006, Jiangsu, Peoples R China.
[5]Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Gastroenterol, Suzhou 215006, Jiangsu, Peoples R China.
[6]Jiangsu Univ, Affiliated Hosp, Dept Gen Surg, Zhenjiang 212001, Jiangsu, Peoples R China.
(8.0+极速模式)