Related Experiment Video
Updated: May 15, 2026
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
MK2 Regulates Ras Oncogenesis through Stimulating ROS Production.
Yusuke Kobayashi1, Xiaomei Qi, Guan Chen
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
Genes & Cancer
|December 25, 2012
Summary
MAPK-activated protein kinase 2 (MK2) has dual roles in Ras oncogenesis, acting as a tumor suppressor in mouse cells but an oncogene in human colon cancer. Its effect depends on reactive oxygen species (ROS) regulation.
Area of Science:
- Cellular biology
- Cancer research
- Signal transduction
Background:
- Ras signaling pathways are crucial in cell growth and cancer development.
- Stress-activated protein kinase pathways, including MAPK-activated protein kinase 2 (MK2), interact with Ras signaling.
- Understanding MK2's role in Ras oncogenesis is vital for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the dual role of MK2 in Ras-driven oncogenesis.
- To elucidate the mechanisms underlying MK2's opposing functions in different cellular contexts.
- To determine the involvement of reactive oxygen species (ROS) in MK2's regulatory effects on Ras oncogenesis.
Main Methods:
- Utilizing MK2 knockout mouse embryonic fibroblasts (MEFs) and human colon cancer cell lines.
- Analyzing Ras transformation and tumor growth in vivo and in vitro.
- Investigating MK2 activation pathways (extracellular signal-regulated kinase, p38α) and ROS levels.
- Employing antioxidant treatments to assess ROS dependency.
Main Results:
- MK2 knockout enhanced Ras transformation and tumor growth in MEFs, suggesting tumor suppressor activity.
- Forced MK2 expression increased, while depletion decreased, malignant growth in human colon cancer cells, indicating oncogenic activity.
- MK2's oncogenic activity correlated with activation by both stress and mitogenic signals, while tumor suppression linked to stress-only activation.
- MK2 differentially regulated ROS levels, decreasing them in MEFs and increasing them in colon cancer cells; ROS were essential for Ras oncogenesis in both.
Conclusions:
- MK2 exhibits context-dependent roles in Ras oncogenesis, functioning as a tumor suppressor or oncogene.
- The opposing functions of MK2 are linked to its differential regulation of ROS production.
- MK2's dual activity highlights the complexity of Ras signaling and offers potential therapeutic targets based on ROS modulation.
More Related Videos
07:13Initiation 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
07:49Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
Related Concept Videos
02:38The 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...
Ras is a superfamily...
03:03mTOR 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...
The mTOR pathway or the...
03:03mTOR 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...
The mTOR pathway or the...
01:07MAPK 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...
01:22PI3K/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 rapamycin-insensitive companion...
01:24Small 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:
Three regulatory proteins control their activity: