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Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Evidence of p38γ and p38δ involvement in cell transformation processes
M Isabel Cerezo-Guisado1, Paloma del Reino, Gaëlle Remy
1Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
Abstract:
The p38 mitogen-activated protein kinase (p38MAPK) signal transduction pathway is an important regulator of cell processes, whose deregulation leads to the development and progression of cancer. Defining the role of each p38MAPK family member in these processes has been difficult. To date, most studies of the p38MAPK pathways focused on function of the p38α isoform, which is widely considered to negatively regulate malignant transformation; nonetheless, few reports address the p38γ and p38δ isoforms. Here, we used embryonic fibroblasts derived from mice lacking p38γ or p38δ and show evidence that these isoforms participate in several processes involved in malignant transformation. We observed that lack of either p38γ or p38δ increased cell migration and metalloproteinase-2 secretion, whereas only p38δ deficiency impaired cell contact inhibition. In addition, lack of p38γ in K-Ras-transformed fibroblasts led to increased cell proliferation as well as tumorigenesis both in vitro and in vivo. Our results indicate that p38γ and p38δ have a role in the suppression of tumor development.
Insights
The p38γ and p38δ isoforms of p38 mitogen-activated protein kinase (p38MAPK) pathway are crucial in suppressing tumor development. Their absence promotes cell migration, proliferation, and tumorigenesis, highlighting their role in cancer suppression.
Area of Science:
- Cellular Biology
- Molecular Oncology
- Signal Transduction Pathways
Background:
- The p38 mitogen-activated protein kinase (p38MAPK) pathway regulates critical cell functions.
- Deregulation of p38MAPK signaling is implicated in cancer development and progression.
- The roles of p38γ and p38δ isoforms in cancer are less understood compared to p38α.
Purpose of the Study:
- To investigate the involvement of p38γ and p38δ isoforms in malignant transformation.
- To define the specific contributions of p38γ and p38δ to processes driving cancer.
- To elucidate the tumor-suppressive functions of p38γ and p38δ.
Main Methods:
- Utilized embryonic fibroblasts from mice genetically deficient in p38γ or p38δ.
- Assessed cell migration, metalloproteinase-2 secretion, and cell contact inhibition in knockout models.
- Evaluated cell proliferation and tumorigenesis in K-Ras-transformed fibroblasts lacking p38γ in vitro and in vivo.
Main Results:
- Absence of either p38γ or p38δ enhanced cell migration and metalloproteinase-2 secretion.
- p38δ deficiency specifically impaired cell contact inhibition.
- Loss of p38γ in K-Ras-transformed cells increased proliferation and tumorigenesis (in vitro and in vivo).
Conclusions:
- p38γ and p38δ isoforms play significant roles in suppressing malignant transformation.
- These isoforms contribute to the regulation of cell migration, proliferation, and contact inhibition.
- The findings reveal a tumor-suppressive function for p38γ and p38δ in the p38MAPK pathway.
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