title: TIG3 tumor suppressor-dependent organelle redistribution and apoptosis in skin cancer cells.
abstract: TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Scharadin
authors.forename: Haibing
authors.initials: H
authors.lastname: Jiang
authors.forename: Ralph
authors.initials: R
authors.lastname: Jans
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Rorke
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002503:Centromere / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008870:Microtubules / Q000378:metabolism; D015388:Organelles / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D016213:Cyclins; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9