Related Experiment Video

Updated: Dec 30, 2025

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

18.5K

Requirement for epithelial p38α in KRAS-driven lung tumor progression

Jessica Vitos-Faleato1, Sebastián M Real1, Nuria Gutierrez-Prat1

  • 1Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.

Proceedings of the National Academy of Sciences of the United States of America
|January 24, 2020
PubMed

Insights

The stress kinase p38α, a tumor suppressor in healthy cells, promotes KrasG12V-driven lung cancer progression. Inhibiting p38α halts tumor growth and improves survival in lung adenocarcinoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Malignant transformation involves altered cell proliferation control via signaling pathways.
  • Cancer cells rely on specific pathways, offering therapeutic targets.
  • The role of stress kinase p38α in cancer is complex and context-dependent.

Purpose of the Study:

  • To investigate the role of p38α in KrasG12V-driven lung cancer.
  • To determine if p38α acts as a tumor suppressor or promoter in lung cancer.
  • To explore therapeutic strategies targeting p38α in lung adenocarcinoma.

Main Methods:

  • In vivo studies using KrasG12V-driven lung cancer mouse models.
  • Analysis of p38α expression levels in patient tumor samples.
  • Genetic and chemical inhibition of p38α.
  • Investigation of p38α's effect on TIMP-1 expression and cell proliferation.

Main Results:

  • p38α acts as a tumor suppressor in healthy lung cells but promotes lung cancer progression.
  • High p38α expression correlates with poor survival in lung adenocarcinoma patients.
  • Inhibition of p38α suppressed tumor growth in mouse models.
  • p38α promotes autocrine cell proliferation by upregulating TIMP-1.

Conclusions:

  • Epithelial p38α is a key driver of KrasG12V-driven lung cancer.
  • p38α maintains self-growth stimulatory signals essential for tumor progression.
  • Targeting p38α represents a potential therapeutic strategy for lung adenocarcinoma.
Keywords:
KRASTIMP-1lung adenocarcinomanononcogene addictionp38α

More Related Videos

Detection of Lung Tumor Progression in Mice by Ultrasound Imaging04:43

Detection of Lung Tumor Progression in Mice by Ultrasound Imaging

Published on: February 27, 2020

7.2K
Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

23.8K

Related Concept Videos

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...
6.9K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.1K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.1K
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...
5.1K
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...
7.7K