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TFE3/PI3K/Akt/mTOR Axis in Renal Cell Carcinoma Affects Tumor Microenvironment

Chungsu Hwang1, Yun Kyung Kang1, Ji Yun Kim1

  • 1Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Korea.

The American Journal of Pathology
|April 8, 2024
PubMed

Insights

Transcription factor E3 (TFE3) influences the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC). Modulating TFE3 affects Akt activity, suggesting PI3K/Akt inhibitors could treat RCC by impacting the tumor microenvironment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is crucial in renal cell carcinoma (RCC) progression, metastasis, and therapy resistance.
  • Transcription factor E3 (TFE3) expression correlates with poor prognosis and influences the tumor microenvironment in RCC patients.

Purpose of the Study:

  • To investigate the relationship between TFE3 expression and the PI3K/Akt pathway in renal cell carcinoma.
  • To elucidate the role of TFE3 in regulating key components of the PI3K/Akt signaling cascade.

Main Methods:

  • Utilized siRNA and shRNA for TFE3 down-regulation and pcDNA3.1 for TFE3 overexpression in UOK146 RCC cells.
  • Administered PI3K and mammalian target of rapamycin (mTOR) inhibitors.
  • Employed Western blot to quantify TFE3, programmed death-ligand 1, phospho-Akt, and Akt levels.

Main Results:

  • TFE3 down-regulation led to a significant increase in phospho-Akt expression.
  • TFE3 overexpression resulted in a significant decrease in phospho-Akt expression.
  • Treatment with a PI3K inhibitor (LY294002) increased TFE3 expression and decreased phospho-Akt levels.

Conclusions:

  • TFE3 plays a significant role in modulating the PI3K/Akt pathway within the context of renal cell carcinoma.
  • Targeting the PI3K/Akt pathway with inhibitors may represent a viable therapeutic strategy for RCC, potentially by altering the tumor microenvironment.

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