Targeting HSP90 Inhibits Proliferation and Induces Apoptosis Through AKT1/ERK Pathway in Lung Cancer

• DOI: 10.3389/fphar.2021.724192
• Publication Date: 2022-01-14T05:43:10Z
• Authors: Mengyuan Niu; Bin Zhang; Li Li; Zhonglan Su; Wenyuan Pu; Chen Zhao; Lulu Wei; Panpan Lian; Renwei Lu; Ranran Wang; Junaid Wazir; Qian Gao; Shiyu Song; Hongwei Wang
• Keywords: Survivin; Hsp90 inhibitor

Lung cancer is one of the most common malignant cancers worldwide. Searching for specific targets and developing efficient therapies with lower toxicity urgently needed. HPS90 a key chaperon protein that has multiple client proteins involved in development cancer. In this study, we investigated transcriptional levels HSP90 isoforms cancerous normal tissues lung patients datasets. The higher expression HSP90AA1 correlated poorer overall survival was observed. transcription activity AKT1/ERK pathways were confirmed patient tissues. both human mouse cell lines, knocking down promoted apoptosis through inhibition pro-survival effect AKT1 by decreasing phosphorylation itself its downstream factors mTOR BAD, as well downregulating Mcl1, Bcl-xl, Survivin. knockdown also suppressed proliferation inhibiting ERK activation CyclinD1 expression. treatment 17-DMAG, an inhibitor, recaptured these effects vitro inhibited tumor growth, induced without obvious side xenograft models. This study suggests targeting 17-DMAG could be potential therapy