title: Fused Toes Homolog modulates radiation cytotoxicity in uterine cervical cancer cells.
abstract: Radiotherapy is the major treatment modality for uterine cervical cancer, but in some cases, the disease is radioresistant. Defining the molecular events that contribute to radioresistance and progression of cancer are of critical importance. Here we evaluated the role of Fused Toes Homolog (FTS) in radiation resistance of cervical carcinoma. Immunostaning of cervical cancer cells and tissues revealed that FTS localization and expression was changed after radiation. Targeted stable knockdown of FTS in HeLa cells led to the growth inhibition after radiation. Radiation induced AKT mediated cytoprotective effect was countered by FTS knockdown which leads to PARP cleavage and caspase-3 activation leading to cell death. FTS knockdown promotes radiation induced cell cycle arrest at G0/G1 and apoptosis of HeLa cells with concurrent alterations in the display of cell cycle regulatory proteins. This study revealed FTS is involved in radioresistance of cervical cancer. Targeted inhibition of FTS led to the shutdown of key elemental characteristics of cervical cancer and could lead to an effective therapeutic strategy.
authors.affiliation: Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 361-763, Republic of Korea.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Anandharaj
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Cinghu
authors.forename: Won-Dong
authors.initials: WD
authors.lastname: Kim
authors.forename: Jae-Ran
authors.initials: JR
authors.lastname: Yu
authors.forename: Woo-Yoon
authors.initials: WY
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017304:Annexin A5 / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D002999:Clone Cells; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011827:Radiation; D011836:Radiation Tolerance; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
chemical_list: C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3