Oncogenic ASPM Is a Regulatory Hub of Developmental and Stemness Signaling in Cancers.

Autor:	Tsai KK; Laboratory of Advanced Molecular Therapeutics, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan., Bae BI; Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut., Hsu CC; School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan., Cheng LH; Laboratory of Advanced Molecular Therapeutics, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Shaked Y; Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.; Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2023 Sep 15; Vol. 83 (18), pp. 2993-3000.
DOI:	10.1158/0008-5472.CAN-23-0158
Abstrakt:	Despite recent advances in molecularly targeted therapies and immunotherapies, the effective treatment of advanced-stage cancers remains a largely unmet clinical need. Identifying driver mechanisms of cancer aggressiveness can lay the groundwork for the development of breakthrough therapeutic strategies. Assembly factor for spindle microtubules (ASPM) was initially identified as a centrosomal protein that regulates neurogenesis and brain size. Mounting evidence has demonstrated the pleiotropic roles of ASPM in mitosis, cell-cycle progression, and DNA double-strand breaks (DSB) repair. Recently, the exon 18-preserved isoform 1 of ASPM has emerged as a critical regulator of cancer stemness and aggressiveness in various malignant tumor types. Here, we describe the domain compositions of ASPM and its transcript variants and overview their expression patterns and prognostic significance in cancers. A summary is provided of recent progress in the molecular elucidation of ASPM as a regulatory hub of development- and stemness-associated signaling pathways, such as the Wnt, Hedgehog, and Notch pathways, and of DNA DSB repair in cancer cells. The review emphasizes the potential utility of ASPM as a cancer-agnostic and pathway-informed prognostic biomarker and therapeutic target. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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