TFE3/PI3K/Akt/mTOR axis in renal cell carcinoma affects tumor microenvironment

Am J Pathol. 2024 Apr 6:S0002-9440(24)00122-6. doi: 10.1016/j.ajpath.2024.02.022. Online ahead of print.ABSTRACTThe role of the PI3K/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been thoroughly investigated. Transcription factor E3 (TFE3) expression is related to poorer prognosis and tumor microenvironment in patients with RCC. We aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 downregulation was achieved by transient transfection of small interfering RNA (siRNA) and short hairpin RNA (shRNA) in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mTOR and PI3K inhibitors. Western blotting was performed to detect TFE3, PD-L1, phospho-Akt (p-Akt), and Akt. p-Akt expression significantly increased upon downregulation of TFE3, and significantly decreased upon upregulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. TFE3 is related to the PI3K/Akt pathway in RCC, and our results suggest that PI3K/Akt inhibitors may potentially aid in treatment of patients with RCC by affecting tumor microenvironment.PMID:38588851 | DOI:10.1016/j.ajpath.2024.02.022
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research