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

Abstract

Through a comprehensive review and in silico analysis of reported data on STATlinked 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.

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

“…This suggests that PRF1 mediates tumor-infiltrating T lymphocytes (TIL) oligoclonal amplification-enhanced Th1 (helper T cell type I)-skewed cellular immunity during nivolumab treatment ( 53 ). STAT1 (signal transducers and activators of transcription 1) is a family of cytosolic proteins that, upon activation, can translocate to the nucleus and bind DNA, which has dual signal transduction and transcriptional control functions ( 54 , 55 ). Hypermethylation in the promoter region of the SOCS3 gene was discovered to reduce SOCS3 protein expression in some CM patients.…”

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

“…This suggests that PRF1 mediates tumor-in ltrating T lymphocytes (TIL) oligoclonal ampli cation-enhanced Th1 (helper T cell type I)-skewed cellular immunity during nivolumab treatment [45]. STAT1 (signal transducers and activators of transcription 1) is a family of cytosolic proteins that, upon activation, can translocate to the nucleus and bind DNA, which has dual signal transduction and transcriptional control functions [46] [47]. Hypermethylation in the promoter region of the SOCS3 gene was discovered to reduce SOCS3 protein expression in some CM patients.…”

Toward the next generation EGFR inhibitors: an overview of osimertinib resistance mediated by EGFR mutations in non-small cell lung cancer

“…[ 33 ]. Last but not least is the JAK/STAT signal transduction pathway, which mainly regulates immunity and mediates the proliferation and invasion of cancer cells [ 34 , 35 ]. These signal transduction pathways have their respective functions and play important roles in promoting transcriptional activation, cell proliferation, mitosis, anti-apoptosis, invasion, and metastasis [ 36 ].…”