Transcription Factor E3/Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Axis in Renal Cell Carcinoma Affects Tumor Microenvironment

Chung Su Hwang; Yun Kyung Kang; Ji Yun Kim; So Hyun Shin; Joon Young Park; Ji Sun Song; So Young Kim; Se Jin Jung; Jung Hee Lee; Ju-Young Na; Dong Hoon Shin; Jee Yeon Kim; Sung Woo Park; Hyun Jung Lee

doi:10.1016/j.ajpath.2024.02.022

Transcription Factor E3/Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin 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.

Authors

Affiliations

¹ Department of Pathology, School of Medicine, Pusan National University Yangsan Hospital, Pusan National University, Yangsan, Korea.
² Department of Pathology, School of Medicine, Pusan National University, Yangsan, Korea.
³ Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Korea.
⁴ Department of Urology, School of Medicine, Pusan National University Yangsan Hospital, Pusan National University, Yangsan, Korea.
⁵ Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea. Electronic address: hyunjunglee@pusan.ac.kr.

PMID: 38588851
DOI: 10.1016/j.ajpath.2024.02.022

Abstract

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and 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 mammalian target of rapamycin and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. 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 the results of this study suggest that PI3K/Akt inhibitors potentially may aid in treatment of patients with RCC by affecting the tumor microenvironment.