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JAK‐STAT core cancer pathway: An integrative cancer interactome analysis

by Israelian, Johan , Qadree, Abdul Khawazak , Araujo, Elvin Dominic , Valent, Peter , Orlova, Anna , Moriggl, Richard , Erdogan, Fettah , Radu, Tudor Bogdan , Herling, Marco , Gunning, Patrick Thomas , Mustjoki, Satu M.

in Addictions / Bioassays / Blood cancer / Breast cancer / Cancer / Cell cycle / Colorectal cancer / colorectal cancers / Communication / Cytokines / Cytokines - metabolism / ErbB Receptors - metabolism / ESR1 protein / Gene expression / Granulocytes / Growth factors / Humans / JAK/STAT pathway in cancers / Kinases / Ligands / Liver cancer / liver cancers / Localization / lung cancer / Mutation / Neoplasms - genetics / Original / Prostate cancer / Proteins / protein‐protein interactions / STAT Transcription Factors - genetics / STAT Transcription Factors - metabolism / Stat1 protein / Stat2 protein / Stat3 protein / Stat4 protein / Stat5 protein / Stat6 protein / systems medicine / Therapeutic targets / Transcription factors / Tumor necrosis factor-TNF / Tumors

2022

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2022

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2022

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Journal Article

JAK‐STAT core cancer pathway: An integrative cancer interactome analysis

Israelian, Johan,

Qadree, Abdul Khawazak,

Araujo, Elvin Dominic,

Valent, Peter,

Orlova, Anna,

Moriggl, Richard,

Erdogan, Fettah,

Radu, Tudor Bogdan,

Herling, Marco,

Gunning, Patrick Thomas,

Mustjoki, Satu M.

2022

Overview

Through a comprehensive review and in silico analysis of reported data on STAT‐linked diseases, we analysed the communication pathways and interactome of the seven STATs in major cancer categories and proposed rational targeting approaches for therapeutic intervention to disrupt critical pathways and addictions to hyperactive JAK/STAT in neoplastic states. Although all STATs follow a similar molecular activation pathway, STAT1, STAT2, STAT4 and STAT6 exert specific biological profiles associated with a more restricted pattern of activation by cytokines. STAT3 and STAT5A as well as STAT5B have pleiotropic roles in the body and can act as critical oncogenes that promote many processes involved in cancer development. STAT1, STAT3 and STAT5 also possess tumour suppressive action in certain mutational and cancer type context. Here, we demonstrated member‐specific STAT activity in major cancer types. Through systems biology approaches, we found surprising roles for EGFR family members, sex steroid hormone receptor ESR1 interplay with oncogenic STAT function and proposed new drug targeting approaches of oncogenic STAT pathway addiction.

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Publisher

John Wiley & Sons, Inc,John Wiley and Sons Inc

Subject

/ Cancer