TTF-1/Nkx2.1 functional connection with mutated EGFR relies on LRIG1 and β-catenin pathways in lung cancer cells
作者： Michela Zamboni , Donato Civitareale
DOI: 10.1016/J.BBRC.2018.10.015
关键词: Biology 、 Catenin 、 Gene expression 、 Transcription factor 、 Lung cancer 、 Small hairpin RNA 、 Antibody 、 Gene 、 Cancer research 、 Adenocarcinoma
摘要: Abstract In non-small lung cancer, the expression of transcription factor TTF-1/Nkx2.1 correlates with presence EGFR mutations, therefore is used to optimize an testing strategy and guide clinical treatment. We investigate molecular mechanisms underlying functional connection between gene in adenocarcinoma. Using H1975 cell line as a cell cancer model system short hairpin RNA, we have selected clones silenced expression. found that Leucine-rich immunoglobulin repeats-1 (LRIG1) direct target binding LRIG1 genomic sequence inhibits its depleted clones, high levels decreased protein. Furthermore, detected reduced β-catenin level provide experimental evidence indicating regulated by β-catenin. Published studies indicate triggers degradation mutated induces activity. Hence, present study show EGFR, enhancing β-catenin, stimulates and, at same time, TTF-1/Nkx2.1, down-regulating LRIG1, sustains pathway. Therefore, mediate EGFR.
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