PURPOSE OF REVIEW: Inflammation is emerging as a new hallmark of cancer, and the toll-like receptor and interleukin-1 receptor adaptor molecule MyD88 has been linked to tumorigenesis. The purpose of this review is to give a brief overview of the latest advances in understanding the complexity of MyD88 implication in tumorigenesis. RECENT FINDINGS: MyD88 is shown to play a protumorigenic role through two mechanisms. First, it activates the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in the hematopoietic compartment and in tumor cells, inducing an inflammatory environment favorable to carcinogenesis. Second, it plays a cell-autonomous role in Ras signaling and transformation, independently of its role in inflammatory signaling. MyD88 mediates the optimal activation of the Ras/extracellular signal-regulated kinase (ERK) pathway by binding to ERK and protecting it from dephosphorylation. This optimal activation of the Ras pathway is essential for the expression of important DNA repair enzymes, allowing cancer cells to efficiently repair damaged DNA. MyD88 is also shown in certain cases to play an antitumoral role through modulation of the immune response SUMMARY: These findings present a new dual function model for MyD88 implication in carcinogenesis making it a potential therapeutic target in cancer.
PURPOSE OF REVIEW: Inflammation is emerging as a new hallmark of cancer, and the toll-like receptor and interleukin-1 receptor adaptor molecule MyD88 has been linked to tumorigenesis. The purpose of this review is to give a brief overview of the latest advances in understanding the complexity of MyD88 implication in tumorigenesis. RECENT FINDINGS:MyD88 is shown to play a protumorigenic role through two mechanisms. First, it activates the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in the hematopoietic compartment and in tumor cells, inducing an inflammatory environment favorable to carcinogenesis. Second, it plays a cell-autonomous role in Ras signaling and transformation, independently of its role in inflammatory signaling. MyD88 mediates the optimal activation of the Ras/extracellular signal-regulated kinase (ERK) pathway by binding to ERK and protecting it from dephosphorylation. This optimal activation of the Ras pathway is essential for the expression of important DNA repair enzymes, allowing cancer cells to efficiently repair damaged DNA. MyD88 is also shown in certain cases to play an antitumoral role through modulation of the immune response SUMMARY: These findings present a new dual function model for MyD88 implication in carcinogenesis making it a potential therapeutic target in cancer.
Authors: Anna Chorzalska; John Morgan; Nagib Ahsan; Diana O Treaba; Adam J Olszewski; Max Petersen; Nathan Kingston; Yan Cheng; Kara Lombardo; Christoph Schorl; Xiaoqing Yu; Roberta Zini; Annalisa Pacilli; Alexander Tepper; Jillian Coburn; Anita Hryniewicz-Jankowska; Ting C Zhao; Elena Oancea; John L Reagan; Olin Liang; Leszek Kotula; Peter J Quesenberry; Philip A Gruppuso; Rossella Manfredini; Alessandro Maria Vannucchi; Patrycja M Dubielecka Journal: Blood Date: 2018-09-13 Impact factor: 22.113
Authors: Paola M Tricarico; Michele Boniotto; Giovanni Genovese; Christos C Zouboulis; Angelo V Marzano; Sergio Crovella Journal: Front Immunol Date: 2019-04-25 Impact factor: 7.561