Silencing Akt1 Inhibits Starvation Induced Lung Metastasis Through Epithelial Mesenchymal Transition Independent of E-cadherin in Prostate Cancer

Abstract

BackgroundEpithelial to mesenchymal transition (EMT) of prostate cancer (PCa) cells facilitates their progress to metastasis. We have recently reported Akt1 is an important EMT regulator, and silencing Akt1 induced EMT and inhibited the growth of PCa cells. These results imply Akt1 silencing may increase starvation resistance of PCa cells. However, little is known about the role of Akt1 of PCa cells in starvation.MethodsApoptosis was detected by TUNEL and flow cytometry, cell invasion was detected by transwells and ECIS, lung metastasis was evaluated by tail vein injection animal model, variation of EMT markers was detected by Western-blot.ResultsWe found starvation slowed down the growth and proliferation, and increased apoptosis of PCa cells; Silencing Akt1 gene inhibited these effects of starvation and decreased E-cadherin. Akt1 silencing enhanced invasion induced by starvation of PCa cells in vitro ; however, it inhibited lung metastasis induced by starvation of PCa cells in vivo unexpectedly.ConclusionStarvation or silencing Akt1 alone can promote lung metastasis of PCa cells, however, silencing Akt1 while starving PCa cells can significantly inhibit this function via EMT independent of E-cadherin.