Interleukin-1 Receptor-Associated Kinase 1 in Cancer Metastasis and Therapeutic Resistance: Mechanistic Insights and Translational Advances.

Authors

• Mariana K Najjar
• Munazza S Khan
• Chuling Zhuang
• Ankush Chandra
• Hui-Wen Lo

Language

English

Publication Date

10-12-2024

Journal

Cells

DOI

10.3390/cells13201690

PMID

39451208

PMCID

PMC11506742

PubMedCentral® Posted Date

10-12-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Interleukin-1 Receptor Associated Kinase 1 (IRAK1) is a serine/threonine kinase that plays a critical role as a signaling transducer of the activated Toll-like receptor (TLR)/Interleukin-1 receptor (IL-1R) signaling pathway in both immune cells and cancer cells. Upon hyperphosphorylation by IRAK4, IRAK1 forms a complex with TRAF6, which results in the eventual activation of the NF-κB and MAPK pathways. IRAK1 can translocate to the nucleus where it phosphorylates STAT3 transcription factor, leading to enhanced IL-10 gene expression. In immune cells, activated IRAK1 coordinates innate immunity against pathogens and mediates inflammatory responses. In cancer cells, IRAK1 is frequently activated, and the activation is linked to the progression and therapeutic resistance of various types of cancers. Consequently, IRAK1 is considered a promising cancer drug target and IRAK1 inhibitors have been developed and evaluated preclinically and clinically. This is a comprehensive review that summarizes the roles of IRAK1 in regulating metastasis-related signaling pathways of importance to cancer cell proliferation, cancer stem cells, and dissemination. This review also covers the significance of IRAK1 in mediating cancer resistance to therapy and the underlying molecular mechanisms, including the evasion of apoptosis and maintenance of an inflammatory tumor microenvironment. Finally, we provide timely updates on the development of IRAK1-targeted therapy for human cancers.

Keywords

Humans, Interleukin-1 Receptor-Associated Kinases, Neoplasm Metastasis, Neoplasms, Drug Resistance, Neoplasm, Signal Transduction, Animals, Translational Research, Biomedical, : IRAK1, metastasis, TLR/IL-1R axis, therapeutic resistance, IRAK1 inhibitors

Published Open-Access

yes

Recommended Citation

Najjar, Mariana K; Khan, Munazza S; Zhuang, Chuling; et al., "Interleukin-1 Receptor-Associated Kinase 1 in Cancer Metastasis and Therapeutic Resistance: Mechanistic Insights and Translational Advances." (2024). Faculty, Staff and Student Publications. 3506.
https://digitalcommons.library.tmc.edu/uthmed_docs/3506