Related Experiment Video
Updated: Mar 8, 2026
07:49
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
6.6K
Mutant RAS Calms Stressed-Out Cancer Cells.
Kirsten L Bryant1, Channing J Der1
1Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Developmental Cell
|January 25, 2017
Summary
Mutant KRAS drives cancer cell lipid production, leading to stress granule formation under stress. This protects cancer cells and creates a resistant tumor microenvironment.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Mutant RAS proteins are key drivers in many human cancers.
- RAS-driven cancers exhibit resistance to conventional chemotherapeutics.
- The cellular mechanisms underlying this resistance are not fully understood.
Purpose of the Study:
- To investigate the role of mutant KRAS in cellular response to stress.
- To elucidate the mechanisms by which mutant KRAS promotes resistance to chemotherapeutics.
- To identify potential therapeutic targets for overcoming RAS-driven cancer resistance.
Main Methods:
- Utilized cell culture models of mutant KRAS-driven cancers.
- Analyzed lipid production pathways in response to cellular stress.
- Investigated the formation and function of stress granules.
- Assessed the impact of stress granule formation on chemotherapeutic sensitivity and tumor microenvironment.
Main Results:
- Mutant KRAS-dependent lipid production is upregulated under cellular stress.
- Increased lipid production leads to the enhanced formation of stress granules.
- Stress granules confer cell-autonomous protection against stress.
- Paracrine signaling from these cells establishes a stress-resistant tumor niche.
Conclusions:
- Mutant KRAS-driven lipid production and subsequent stress granule formation are critical for cancer cell survival under stress.
- This mechanism contributes to both intrinsic and extrinsic resistance to chemotherapeutics.
- Targeting KRAS-mediated lipid metabolism or stress granule pathways may offer novel therapeutic strategies for RAS-driven cancers.
Related Concept Videos
02:38The Ras Gene
7.4K
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...
Ras is a...
7.4K
01:24Small GTPases - Ras and Rho
5.6K
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:
Three regulatory proteins control their activity:
5.6K
02:23Abnormal Proliferation
5.3K
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...
5.3K
02:53Adaptive Mechanisms in Cancer Cells
7.2K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.2K
03:03mTOR Signaling and Cancer Progression
5.0K
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 mTOR pathway or the...
5.0K
01:19Psychoneuroimmunology: Diabetes and Cancer
568
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
568