title: The interplay between centrosomes and the Hippo tumor suppressor pathway.
abstract: Centrosome amplification is a common feature of both solid and hematological human malignancies. Extra centrosomes are not merely innocent bystanders in cancer cells, but rather promote tumor progression by disrupting normal cellular architecture and generating chromosome instability. Consequently, centrosome amplification correlates with advanced tumor grade and overall poor clinical prognosis. By contrast, extra centrosomes are adversely tolerated in non-transformed cells and hinder cell proliferation. This suggests that in addition to acquiring extra centrosomes, cancer cells must also adapt to overcome the deleterious consequences associated with them. Here, we review evidence that implicates core components of the Hippo tumor suppressor pathway as having key roles in both the direct and indirect regulation of centrosome number. Intriguingly, functional inactivation of the Hippo pathway, which is common across broad spectrum of human cancers, likely represents one key adaptation that enables cancer cells to tolerate extra centrosomes.
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Division of Hematology and Oncology, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Bolgioni
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Division of Hematology and Oncology, Boston University School of Medicine, Boston, MA, 02118, USA. nganem@bu.edu.|Department of Medicine, Division of Hematology and Oncology, Boston University School of Medicine, Boston, MA, 02118, USA. nganem@bu.edu.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Ganem
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism*; D000090683:Hippo Signaling Pathway; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases
keywords: LATS; MST; TAZ; Tetraploid; YAP; p53