Related Experiment Video

Updated: Jul 7, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Mining for JAK-STAT mutations in cancer

Stefan N Constantinescu1, Michael Girardot, Christian Pecquet

  • 1Ludwig Institute for Cancer Research and de Duve Institute, Université catholique de Louvain, Brussels B-1200, Belgium. stefan.constantinescu@bru.licr.org

Trends in Biochemical Sciences
|February 23, 2008
PubMed

Insights

Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway mutations, particularly in JAK2, are implicated in myeloproliferative neoplasms and other cancers. These mutated JAK proteins represent promising targets for novel anti-cancer therapies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is crucial for cytokine signaling, regulating cell survival, proliferation, and differentiation.
  • Constitutive activation of the JAK-STAT pathway, often due to JAK or STAT mutations, is observed in various cancers.

Purpose of the Study:

  • To investigate the role of JAK-STAT pathway mutations in cancer development.
  • To identify specific JAK mutations associated with myeloproliferative neoplasms and other malignancies.
  • To explore the therapeutic potential of targeting mutated JAK proteins in cancer treatment.

Main Methods:

  • Analysis of patient samples for JAK and STAT mutations.
  • Functional studies to assess the impact of identified mutations on JAK-STAT pathway signaling.
  • Evaluation of mutated JAK proteins as therapeutic targets.

Main Results:

  • A specific somatic mutation in JAK2 (V617F) was identified in a majority of patients with myeloproliferative neoplasms, leading to cytokine-independent JAK2 activation.
  • Mutations in JAK2 and JAK3 were also found in a minority of patients with polycythemia vera and acute megakaryoblastic leukemia.
  • These findings suggest that further JAK-STAT pathway mutations will be discovered in diverse cancers.

Conclusions:

  • Mutations in the JAK-STAT pathway, especially in JAK2, are significant drivers in certain cancers.
  • Mutated JAK proteins are emerging as critical targets for the development of new anti-cancer drugs.

More Related Videos

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells07:12

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells

Published on: September 9, 2021

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The 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...
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...
Abnormal Proliferation02:23

Abnormal 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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/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...
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.