title: Molecular Pathways: New Signaling Considerations When Targeting Cytoskeletal Balance to Reduce Tumor Growth.
abstract: The dynamic balance between microtubule extension and actin contraction regulates mammalian cell shape, division, and motility, which has made the cytoskeleton an attractive and very successful target for cancer drugs. Numerous compounds in clinical use to reduce tumor growth cause microtubule breakdown (vinca alkaloids, colchicine-site, and halichondrins) or hyperstabilization of microtubules (taxanes and epothilones). However, both of these strategies indiscriminately alter the assembly and dynamics of all microtubules, which causes significant dose-limiting toxicities on normal tissues. Emerging data are revealing that posttranslational modifications of tubulin (detyrosination, acetylation) or microtubule-associated proteins (Tau, Aurora kinase) may allow for more specific targeting of microtubule subsets, thereby avoiding the broad disruption of all microtubule polymerization. Developing approaches to reduce tumor cell migration and invasion focus on disrupting actin regulation by the kinases SRC and ROCK. Because the dynamic balance between microtubule extension and actin contraction also regulates cell fate decisions and stem cell characteristics, disrupting this cytoskeletal balance could yield unexpected effects beyond tumor growth. This review will examine recent data demonstrating that cytoskeletal cancer drugs affect wound-healing responses, microtentacle-dependent reattachment efficiency, and stem cell characteristics in ways that could affect the metastatic potential of tumor cells, both beneficially and detrimentally.
authors.affiliation: Marlene and Stewart Greenebaum NCI Cancer Center, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA.|Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Kristi R
authors.initials: KR
authors.lastname: Chakrabarti
authors.affiliation: Marlene and Stewart Greenebaum NCI Cancer Center, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA.|General Surgery Residency Program, University of Maryland Medical Center, 22 S. Greene Street, Baltimore, MD 21201, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hessler
authors.affiliation: Marlene and Stewart Greenebaum NCI Cancer Center, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA.|Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Lekhana
authors.initials: L
authors.lastname: Bhandary
authors.affiliation: Marlene and Stewart Greenebaum NCI Cancer Center, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA.|Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.|Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Martin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents