Related Experiment Video

Updated: Jul 18, 2026

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

RAS unplugged: negative feedback and oncogene-induced senescence

Nabeel Bardeesy1, Norman E Sharpless

  • 1Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA. nelbardeesy@partners.org

Cancer Cell
|December 13, 2006
PubMed

Insights

Oncogene activation triggers senescence, a tumor suppressor program. New findings reveal RAS/RAF pathway activation reduces MAPK and PI3K signaling, which is essential for this growth arrest.

Area of Science:

  • Cellular biology
  • Oncology
  • Molecular signaling

Background:

  • Senescence is a tumor suppressor mechanism where normal cells permanently arrest growth in response to stress like oncogene activation.
  • Sustained activation of MAP kinase (MAPK) and PI3 kinase (PI3K) signaling was previously thought to drive oncogene-induced senescence.

Purpose of the Study:

  • To investigate the signaling pathways involved in oncogene-induced senescence.
  • To challenge the prevailing model of senescence induction.

Main Methods:

  • Investigated the effects of aberrant RAS/RAF pathway activation on MAPK and PI3K signaling.
  • Analyzed the role of signaling attenuation in senescence.

Main Results:

  • Aberrant RAS/RAF pathway activation initiates a negative feedback loop.
  • This feedback loop globally attenuates MAPK and PI3K signaling.
  • Reduced MAPK and PI3K signaling is a prerequisite for senescence.

Conclusions:

  • The established model of senescence induction via sustained MAPK/PI3K signaling is challenged.
  • RAS/RAF pathway activation-mediated attenuation of MAPK/PI3K signaling is critical for senescence.
  • Senescence is a complex process involving feedback mechanisms that regulate key signaling pathways.

More Related Videos

Techniques to Induce and Quantify Cellular Senescence06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle09:14

Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle

Published on: October 26, 2017

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 superfamily...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.