Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel.
Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models. Here, we describe the identification of candidate Fhit-interacting proteins with cytosolic and plasma membrane localization. Among these, Annexin 4 (ANXA4) was validated by co-immunoprecipitation and confocal microscopy as a partner of this novel Fhit protein complex. Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel. Moreover, paclitaxel administration in combination with AdFHIT acts synergistically to increase the apoptotic rate of tumor cells both in vitro and in vivo experiments.
Department of Molecular Immunology, Virology and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America ; Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland ; Dipartimento di Medicina Sperimentale e Clinica, University Magna Græcia, Campus "S. Venuta", Catanzaro, Italy.
Eugenio
E
Gaudio
Francesco
F
Paduano
Riccardo
R
Spizzo
Apollinaire
A
Ngankeu
Nicola
N
Zanesi
Marco
M
Gaspari
Francesco
F
Ortuso
Francesca
F
Lovat
Jonathan
J
Rock
Grace A
GA
Hill
Mohamed
M
Kaou
Giovanni
G
Cuda
Rami I
RI
Aqeilan
Stefano
S
Alcaro
Carlo M
CM
Croce
Francesco
F
Trapasso
D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017314:Annexin A4 / Q000235:genetics / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D047468:Immunoprecipitation; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology*; D021381:Protein Transport; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D017314:Annexin A4; D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D017239:Paclitaxel; D000099170:Bis(5'-adenosyl)triphosphatase