Related Experiment Video
Updated: Aug 11, 2026
11:19
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity
1Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Oncogene
|August 9, 2001
Summary
Activating mutations in c-kit (Asp(816)) drive cancers like AML. This study reveals that Signal Transducer and Activator of Transcription 3 (STAT3) activation by mutant c-Kit is essential for tumor growth and survival.
Area of Science:
- Molecular Biology
- Oncology
- Signal Transduction
Background:
- Activating mutations in c-kit at codon 816 (Asp(816)) are implicated in various malignancies, including acute myeloid leukemia (AML) and mastocytosis.
- Mutant c-Kit receptor signaling leads to cytokine independence and promotes tumorigenicity, but the underlying molecular mechanisms remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms by which Asp(816) mutant c-Kit induces tumorigenicity.
- To investigate the role of signal transduction pathways, specifically STAT proteins, in mediating the effects of mutant c-Kit.
Main Methods:
- Utilized the human embryonic kidney 293 cell line for experiments.
- Investigated the association between D816H mutant c-Kit and the activation of STAT3 and STAT1.
- Employed dominant-negative STAT3 and STAT1 transfections to assess their role in anchorage-independent growth and tumor formation.
- Examined the effect of constitutively activated STAT3 expression on mutant c-Kit's transforming ability.
Main Results:
- Constitutive activation of STAT3 and STAT1 was observed in association with D816H mutant c-Kit.
- Inhibition of STAT3, but not STAT1, using dominant-negative constructs significantly reduced mutant c-Kit-mediated anchorage-independent growth and in vivo tumor formation.
- Restoration of constitutively activated STAT3 expression re-established the transforming ability of the mutant c-Kit receptor in 293 cells.
Conclusions:
- Activation of STAT3 by Asp(816) mutant c-Kit is a critical requirement for anchorage-independent growth.
- STAT3 activation is essential for the tumorigenicity induced by Asp(816) mutant c-Kit.
- These findings highlight STAT3 as a key mediator of oncogenic signaling downstream of mutant c-Kit.
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...
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...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
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...
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...