Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid Anhydride Hydrolases / genetics
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Acid Anhydride Hydrolases / metabolism*
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Amino Acid Sequence
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Animals
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Annexin A4 / genetics
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Annexin A4 / metabolism*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Line, Tumor
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Cell Membrane / metabolism
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Cytosol / metabolism
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Gene Expression
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Humans
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Immunoprecipitation
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Injections, Intravenous
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Microscopy, Confocal
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Molecular Sequence Data
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neoplasm Transplantation
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Paclitaxel / pharmacology*
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Protein Transport
Substances
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Annexin A4
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Antineoplastic Agents, Phytogenic
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Neoplasm Proteins
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fragile histidine triad protein
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Acid Anhydride Hydrolases
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Paclitaxel