BTK: a two-faced effector in cancer and tumour suppression

• Published in: Cell death & disease Vol. 9; no. 11; pp. 1064 - 3
• Main Authors: Rada, Miran, Barlev, Nickolai, Macip, Salvador
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.10.2018; Springer Nature B.V
• Subjects: 96/109; 96/2; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Agammaglobulinaemia Tyrosine Kinase - genetics; Agammaglobulinaemia Tyrosine Kinase - metabolism; Antibodies; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; B-Lymphocytes - drug effects; B-Lymphocytes - enzymology; B-Lymphocytes - pathology; Biochemistry; Biomedical and Life Sciences; Bruton's tyrosine kinase; Cancer; Cell Biology; Cell Culture; Cell Survival - drug effects; Cell Survival - genetics; Comment; Gene Expression Regulation, Neoplastic; Genomes; Humans; Immunology; Life Sciences; Lymphocytes B; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - pathology; p53 Protein; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phospholipase C gamma - genetics; Phospholipase C gamma - metabolism; Phosphorylation - drug effects; Pleiotropy; Protein Kinase Inhibitors - pharmacology; Protein-tyrosine kinase; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Signal Transduction; Tumor Protein p73 - genetics; Tumor Protein p73 - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-1122-8

Many genes of the human genome display pleiotropic activity, playing an important role in two or more unrelated pathways. Surprisingly, some of these functions can even be antagonistic, often letting to divergent functional outcomes depending on microenviromental cues and tissue/cell type-dependent parameters. Lately, the Bruton’s tyrosine kinase (BTK) has emerged as one of such pleiotropic genes, with opposing effects in cancer pathways. While it has long been considered oncogenic in the context of B cell malignancies, recent data shows that BTK can also act as a tumour suppressor in other cells, as an essential member of the p53 and p73 responses to damage. Since BTK inhibitors are already being used clinically, it is important to carefully review these new findings in order to fully understand the consequences of blocking BTK activity in all the cells of the organism.