Related Experiment Video

Updated: Jul 3, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis

Jayashree Joshi1, Pablo J Fernandez-Marcos, Anita Galvez

  • 1Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

The EMBO Journal
|July 25, 2008
PubMed

Insights

The atypical PKC-interacting protein Par-4 (partner of Akt-1) suppresses lung cancer by inhibiting cell survival. Its absence promotes Ras-induced lung carcinoma by enhancing Akt activation, identifying Par-4 as a novel tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The atypical PKC-interacting protein, Par-4, is known to inhibit cell survival and tumorigenesis.
  • Genetic inactivation of Par-4 in mice results in reduced lifespan and enhanced tumor development.

Purpose of the Study:

  • To investigate the role of Par-4 in lung cancer.
  • To elucidate the mechanism by which Par-4 regulates Akt activation in lung tumorigenesis.

Main Methods:

  • Analysis of Par-4 expression in normal lung and human lung cancer samples.
  • In vivo studies using a mouse model of Ras-induced lung tumors.
  • Cell culture and biochemical experiments to determine the interaction between Par-4, PKCzeta, and Akt.

Main Results:

  • Par-4 expression is reduced in human lung cancer compared to normal lung tissue.
  • Lack of Par-4 significantly enhances Ras-induced lung carcinoma formation in mice.
  • Par-4 negatively regulates Akt activation, and this regulation is mediated by PKCzeta.

Conclusions:

  • Par-4 acts as a novel tumor suppressor in the context of lung cancer.
  • Par-4 inhibits Ras-induced lung carcinogenesis by suppressing Akt activation via PKCzeta.
  • These findings establish a new paradigm for Akt regulation and lung cancer development.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...