Related Experiment Video
Updated: Jul 12, 2026
07:38
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Ras pathway activation in malignant mesothelioma.
Manish R Patel1, Blake A Jacobson, Arpita De
1Division of Hematology-Oncology-Transplant, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Summary
Ras signaling pathway activation is elevated in malignant mesothelioma, driving cancer cell proliferation. Inhibiting specific kinases, like c-Jun N-terminal kinase, suppressed proliferation and cap-dependent translation, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Ras family gene mutations are infrequent in malignant mesothelioma.
- The precise role of Ras signaling pathway activation in mesothelioma pathogenesis remains unclear.
Purpose of the Study:
- To investigate the activation status of the Ras pathway and associated kinases in mesothelioma.
- To evaluate the impact of inhibiting specific kinase pathways on mesothelioma cell proliferation.
- To explore the role of kinase signaling in regulating cap-dependent translation.
Main Methods:
- Analysis of Ras pathway activation and associated kinases in human mesothelioma cell lines.
- Treatment of mesothelioma cells with kinase pathway inhibitors (e.g., U0126, SP600125).
- Assessment of cell proliferation and cap-dependent translation markers (e.g., 4E-BP1 phosphorylation).
Main Results:
- Mesothelioma cell lines exhibited higher Ras-guanosine triphosphate (GTP) levels compared to normal cells.
- Key Ras effectors, including extracellular-regulated kinase 1/2 and c-Jun N-terminal kinase, were active in most mesothelioma cell lines.
- Inhibition of extracellular-regulated kinase 1/2 and c-Jun N-terminal kinase reduced mesothelioma cell proliferation; c-Jun N-terminal kinase inhibition specifically decreased 4E-BP1 phosphorylation and cap-dependent translation.
Conclusions:
- Ras and associated signaling pathways represent potential therapeutic targets for malignant mesothelioma.
- Ras-induced proliferation in mesothelioma may occur via mechanisms involving cap-dependent translation.
Related Concept Videos
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...
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...
01:22PI3K/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...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:23Abnormal Proliferation
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 daughter...