Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence
Open accessAbstract
Oncogene-induced senescence (OIS) is a tumor-suppressing response that must be disrupted for cancer to develop. Mechanistic insights into OIS have begun to emerge. Activation of the p53/p21(WAF1) and/or p16(INK4A) tumor-suppressor pathways is essential for OIS. Moreover, the DNA damage response, chromatin remodeling, and senescence-associated secretory phenotype (SASP) are important for the initiation and maintenance of OIS. This review discusses recent advances in elucidating the mechanisms of OIS, focusing on the roles of the p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/cellular homolog of murine thymoma virus AKT/mammalian target of rapamycin (mTOR) pathways. These studies indicate that OIS is mediated by an intricate signaling network. Further delineation of this network may lead to development of new cancer therapies targeting OIS.
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Intermediate senescence was characterized by metabolic changes (citric acid cycle and respiratory electron transport), p53-associated pathways, and p38-gamma/p38-delta signaling.
“Intermediate senescence was characterized by metabolic changes (the citric acid cycle and respiratory electron transport), p53-associated pathways, and signaling mediated by p38-gamma and p38-delta, two isoforms of p38-MAPK (mitogen-activated protein kinase) known to have an important role in senescence and the SASP [38].”
From Unmasking Transcriptional Heterogeneity in Senescent Cells (2017) · cites this paper as [38]
The citation is attached to the statement about p38γ and p38δ, not the citing authors’ characterization of intermediate senescence. In “Differential roles of p38 isoforms in OIS” (page unavailable), the review identifies both as p38 isoforms that mediate oncogene-induced senescence. The passages on the senescence-associated secretory phenotype do not establish a role for these two isoforms in the SASP. (LLM, conf=0.84)
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- Authors
- Xu, Y., Li, N., Xiang, R., & Sun, P.
- Affiliations
- Scripps Research Institute (US)
- Nankai University (CN)
- Corresponding author
- Sun, Peiqing
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 39
- Issue
- 6
- Pages
- 268-276
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC4358807
- OpenAlex
- W1976973627
- Cited by
- 282
- References
- 73
- Citations by year
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- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA172115, R01CA106768, R01CA131231, CA131231, R01CA172115, CA106768)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- oncogene-induced senescence, p38 MAPK, PI3K/AKT/mTOR pathway, senescence-associated secretory phenotype, DNA damage response, chromatin remodeling, p53/p21 pathway, p16INK4a, tumor suppression, cancer therapy targets
- MeSH terms
- Animals, Humans, Oncogenes, Signal Transduction, Cellular Senescence, Phosphatidylinositol 3-Kinases, p38 Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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