Open AccessJAK‐STAT core cancer pathway: An integrative cancer interactome analysis
Author(s) -
Erdogan Fettah,
Radu Tudor Bogdan,
Orlova Anna,
Qadree Abdul Khawazak,
Araujo Elvin Dominic,
Israelian Johan,
Valent Peter,
Mustjoki Satu M.,
Herling Marco,
Moriggl Richard,
Gunning Patrick Thomas
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17228
Subject(s) - stat2 , stat , biology , interactome , stat1 , cancer , stat6 , cancer research , stat5 , context (archaeology) , stat4 , stat3 , jak stat signaling pathway , signal transduction , computational biology , transcription factor , genetics , receptor tyrosine kinase , gene , paleontology
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.