Gomez Solsona Beatriz, Schmitt Anja, Schulze-Osthoff Klaus, Hailfinger Stephan
Interfaculty Institute of Biochemistry, University of Tuebingen, 72076 Tuebingen, Germany.
Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
Biomedicines. 2022 Feb 1;10(2):344. doi: 10.3390/biomedicines10020344.
Almost twenty years ago, the importance of the paracaspase MALT1 in antigen receptor-induced NF-κB activation was first described. Since then, several other immune receptors, G-protein-coupled receptors, and receptor tyrosine kinases were identified as relying on MALT1 to induce NF-κB activation. In various hematological malignancies and solid tumors, MALT1 is constitutively activated and drives chronic NF-κB target gene expression. Deregulated MALT1 activity in cancer thus promotes tumor cell survival, proliferation, and metastasis. Since the molecular function of MALT1 partially requires its protease activity, pharmacological targeting of MALT1 may represent a promising anti-cancer strategy. Here, we review the molecular features of MALT1 activation and function as well as the therapeutic potential of MALT1 inhibition in hematological malignancies and solid tumors.
大约二十年前，首次描述了旁胱天蛋白酶MALT1在抗原受体诱导的NF-κB激活中的重要性。从那时起，其他几种免疫受体、G蛋白偶联受体和受体酪氨酸激酶被确定依赖MALT1来诱导NF-κB激活。在各种血液系统恶性肿瘤和实体瘤中，MALT1被组成性激活并驱动慢性NF-κB靶基因表达。因此，癌症中MALT1活性失调促进肿瘤细胞存活、增殖和转移。由于MALT1的分子功能部分需要其蛋白酶活性，MALT1的药物靶向可能代表一种有前景的抗癌策略。在这里，我们综述了MALT1激活和功能的分子特征以及MALT1抑制在血液系统恶性肿瘤和实体瘤中的治疗潜力。
