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How does the JAK-STAT signaling pathway relate to oncogenes?

Reference

Advertisement The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors Cell Communication and Signaling volume 22, Article number: 68 (2024) Cite this article 165 Accesses 1 Altmetric Metrics details Abstract Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. Provided by the Springer Nature SharedIt content-sharing initiative Keywords Advertisement ISSN: 1478-811X Follow BMC By using this website, you agree to our Terms and Conditions, Your US state privacy rights, Privacy statement and Cookies policy. 2017;3:816–27. Article CAS PubMed PubMed Central Google Scholar Yagil Z, Nechushtan H, Kay G, Yang CM, Kemeny DM, Razin E. The enigma of the role of protein inhibitor of activated STAT3 (PIAS3) in the immune response. 2014;21:443–8. Article CAS PubMed PubMed Central Google Scholar Radtke S, Haan S, Jörissen A, Hermanns HM, Diefenbach S, Smyczek T, Schmitz-Vandeleur H, Heinrich PC, Behrmann I, Haan C. The Jak1 SH2 domain does not fulfill a classical SH2 function in Jak/STAT signaling but plays a structural role for receptor interaction and up-regulation of receptor surface expression. 2022;11:4526–43. Article CAS PubMed PubMed Central Google Scholar Jia Z, Xie Y, Wu H, Wang Z, Li A, Li Z, Yang Z, Zhang Z, Xing Z, Zhang X. Phlorizin from sweet tea inhibits the progress of Esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.

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biosignaling.biomedcentral.com

The activated JAK kinase then phosphorylates specific STATs. STAT proteins dimerise and translocate into the nucleus upon phosphorylation by JAK, where they bind to DNA and regulate transcription. Overactivation of the JAK-STAT pathway can cause cancer by bypassing apoptosis and cell cycle checkpoints.

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onlinelibrary.wiley.com

Signaling via the JAK-STAT pathway causes, with the exception of mutations, autoactivation of JAK kinases induced by ligand binding, resulting in receptor dimerization and cross-phosphorylation of associated JAK kinases that get activated in a sliding mode, where the JH1 and JH2 domains of juxtaposed JAK kinases move away to allow for kinase

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www.sciencedirect.com

OpenAI's Answer

The JAK-STAT signaling pathway plays a critical role in cell growth, survival, differentiation, and immune response, and it is frequently implicated in cancer development and progression. Here's how it is related to oncogenes:

  1. Overactivation and Cancer: The JAK-STAT pathway can become oncogenic when it is aberrantly activated. Overactivation of this pathway bypasses the normal cell cycle checkpoints and apoptosis, leading to uncontrolled cell proliferation, which is a hallmark of cancer source.

  2. Mutation-Induced Activation: In cancer, mutations in JAK kinases can lead to their autoactivation without the normal ligand-induced signaling events. This results in continuous activation of the downstream STAT proteins, contributing to oncogenesis source.

  3. Involvement in Hematological Malignancies: Specifically, the JAK-STAT pathway is known to be heavily implicated in hematological malignancies. This pathway has a central role in cytokine signaling, which is crucial for cell proliferation, survival, and immune response, thus its dysregulation contributes to the malignancy source.

  4. Inflammation and Cancer Linkage: The JAK-STAT pathway also links inflammation with cancer development, tumor progression, and therapy resistance. For example, its activation can lead to the expression of proteins that help tumors evade the immune system’s cytotoxic responses source.

For visual insights, here is a representation of the JAK-STAT signaling pathway: JAK-STAT Signaling Pathway

The interplay between the JAK-STAT pathway and oncogenesis underscores its potential as a target for cancer therapies, aiming to inhibit aberrant signaling and thereby control cancer progression.

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