title: TRIM8 anti-proliferative action against chemo-resistant renal cell carcinoma.
abstract: In some tumours, despite a wild-type p53 gene, the p53 pathway is inactivated by alterations in its regulators or by unknown mechanisms, leading to resistance to cytotoxic therapies. Understanding the mechanisms of functional inactivation of wild-type p53 in these tumours may help to define prospective targets for treating cancer by restoring p53 activity. Recently, we identified TRIM8 as a new p53 modulator, which stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. In this paper we demonstrated that TRIM8 deficit dramatically impairs p53-mediated cellular responses to chemotherapeutic drugs and that TRIM8 is down regulated in patients affected by clear cell Renal Cell Carcinoma (ccRCC), an aggressive drug-resistant cancer showing wild-type p53. These results suggest that down regulation of TRIM8 might be an alternative way to suppress p53 activity in RCC. Interestingly, we show that TRIM8 expression recovery in RCC cell lines renders these cells sensitive to chemotherapeutic treatments following p53 pathway re-activation. These findings provide the first mechanistic link between TRIM8 and the drug resistance of ccRCC and suggest more generally that TRIM8 could be used as enhancer of the chemotherapy efficacy in cancers where p53 is wild-type and its pathway is defective.
authors.affiliation: Institute for Biomedical Technologies ITB, Bari, Italy. Contributed equally to this work.
authors.forename: Mariano Francesco
authors.initials: MF
authors.lastname: Caratozzolo
authors.affiliation: Institute of Biomembranes and Bioenergetics IBBE, Bari, Italy. Contributed equally to this work.
authors.forename: Alessio
authors.initials: A
authors.lastname: Valletti
authors.affiliation: Dept Biomedical Science, University of Foggia, Foggia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Gigante
authors.affiliation: Dept Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro", Bari, Italy.
authors.forename: Italia
authors.initials: I
authors.lastname: Aiello
authors.affiliation: Dept Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro", Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mastropasqua
authors.affiliation: Institute for Biomedical Technologies ITB, Bari, Italy.
authors.forename: Flaviana
authors.initials: F
authors.lastname: Marzano
authors.affiliation: Dept Emergency and Organ Transplantation DETO, University of Bari "A. Moro", Bari, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ditonno
authors.affiliation: Dept Surgical Science, University of Foggia, Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carrieri
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, Faculté de Médecine Lyon-Est, LYON Cedex 08 France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Simonnet
authors.affiliation: Dept Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro", Bari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Erchia
authors.affiliation: Dept Biomedical Science, University of Foggia, Foggia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ranieri
authors.affiliation: Institute of Biomembranes and Bioenergetics IBBE, Bari, Italy. Dept Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "A. Moro", Bari, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.affiliation: Institute for Biomedical Technologies ITB, Bari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sbisà
authors.affiliation: Institute for Biomedical Technologies ITB, Bari, Italy.
authors.forename: Apollonia
authors.initials: A
authors.lastname: Tullo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C418604:TRIM8 protein, human; D016159:Tumor Suppressor Protein p53