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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

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Crosstalk between PKCα and PI3K/AKT Signaling Is Tumor Suppressive in the Endometrium

Alice H Hsu1, Michelle A Lum1, Kang-Sup Shim2

  • 1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Cell Reports
|July 19, 2018
PubMed

Insights

Protein Kinase C alpha (PKCα) suppresses endometrial tumors by inhibiting AKT signaling. Loss of PKCα promotes aggressive cancer, highlighting its tumor-suppressive role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Protein Kinase C (PKC) isozymes are often viewed as oncoproteins.
  • Emerging evidence suggests PKC can act as a tumor suppressor in certain cancers.
  • This study investigates the role of PKCα in endometrial cancer.

Purpose of the Study:

  • To determine if PKCα functions as a tumor suppressor in PI3K/AKT-driven endometrial cancer.
  • To investigate the molecular mechanisms underlying PKCα's tumor suppressive activity.
  • To explore the clinical relevance of PKCα expression in endometrial tumors.

Main Methods:

  • Analysis of human endometrial tumor data for PKCα expression.
  • Utilized murine models to study the effects of PKCα loss on tumor initiation.
  • Investigated the signaling pathways affected by PKCα, including AKT and PP2A.

Main Results:

  • PKCα acts as a tumor suppressor in PI3K/AKT-driven endometrial cancer.
  • Transcriptional suppression of PKCα correlates with aggressive disease and poor prognosis.
  • Loss of PKCα is critical for endometrial tumor initiation in preclinical models.
  • PKCα suppresses tumors via PP2A-dependent inactivation of AKT, even with PI3K/AKT pathway mutations.

Conclusions:

  • PKCα is a critical tumor suppressor in the endometrium.
  • Deregulation of the PKCα→PP2A signaling axis contributes to endometrial tumorigenesis.
  • Targeting this pathway may offer therapeutic strategies for endometrial cancer.
Keywords:
AKTId1PI3KPKCPKCαPP2A familyPTENendometrial cancerendometriumtumor suppression

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