onc2015394.pdf (3.3 MB)
Tumour-suppression function of KLF12 through regulation of anoikis
journal contributionposted on 2020-07-28, 12:24 authored by N Godin-Heymann, S Brabetz, MM Murillo, M Saponaro, CR Santos, A Lobley, P East, P Chakravarty, N Matthews, G Kelly, S Jordan, E Castellano, J Downward
Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental cells results in decreased apoptosis following cell detachment from matrix. KLF12 regulates anoikis by promoting the cell cycle transition through S phase and therefore cell proliferation. Reduced expression levels of KLF12 results in increased ability of lung cancer cells to form tumours in vivo and is associated with poorer survival in lung cancer patients. We therefore identify KLF12 as a novel metastasis-suppressor gene whose loss of function is associated with anoikis resistance through control of the cell cycle.
A549 CellsAnimalsAnoikisCell CycleCell Line, TumorCell ProliferationDown-RegulationFlow CytometryGene Expression Regulation, NeoplasticHumansKruppel-Like Transcription FactorsLung NeoplasmsMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm MetastasisRNA InterferenceReverse Transcriptase Polymerase Chain ReactionSurvival AnalysisTransplantation, HeterologousTumor Suppressor ProteinsDownwardSvejstrupCBASHTS-ackGEP-ackCS-ackFC-ack1112 Oncology and Carcinogenesis1103 Clinical SciencesOncology & Carcinogenesis