STAT6

Context (archaeology)

Receptor tyrosine kinase

STAT2

Cancer research

STAT5

Biology

Gene

Cancer

STAT3

Signal transduction

stat

Computational biology

Interactome

Transcription factor

Paleontology

JAK-STAT signaling pathway

STAT1

Genetics

STAT4

Journal of Cellular and Molecular Medicine

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.

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