Abstract
Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer.
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology
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Antineoplastic Agents / pharmacology*
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Apoptosis / physiology
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Cell Growth Processes / physiology
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Cell Line, Tumor
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Cisplatin / pharmacology*
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DNA Damage
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Down-Regulation
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Humans
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors / biosynthesis*
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Kruppel-Like Transcription Factors / genetics
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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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Prognosis
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Protein Isoforms
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Proto-Oncogene Proteins / biosynthesis*
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Proto-Oncogene Proteins / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Transfection
Substances
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Antineoplastic Agents
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KLF6 protein, human
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors
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Protein Isoforms
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Proto-Oncogene Proteins
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RNA, Messenger
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RNA, Small Interfering
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Cisplatin