title: Tumour-suppression function of KLF12 through regulation of anoikis.
abstract: 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.
authors.affiliation: Signal Transduction, Cancer Research UK London Research Institute, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Godin-Heymann
authors.affiliation: Signal Transduction, Cancer Research UK London Research Institute, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Brabetz
authors.affiliation: Signal Transduction, Cancer Research UK London Research Institute, London, UK.|The Institute of Cancer Research, London, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Murillo
authors.affiliation: Mechanisms of Gene Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Hertfordshire, UK.
authors.forename: M
authors.initials: M
authors.lastname: Saponaro
authors.affiliation: Translational Cancer Therapeutics, Cancer Research UK London Research Institute, London, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Santos
authors.affiliation: Bioinformatics and Biostatistics Laboratories, Cancer Research UK London Research Institute, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lobley
authors.affiliation: Bioinformatics and Biostatistics Laboratories, Cancer Research UK London Research Institute, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: East
authors.affiliation: Bioinformatics and Biostatistics Laboratories, Cancer Research UK London Research Institute, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Chakravarty
authors.affiliation: Advanced Sequencing Facility, Cancer Research UK London Research Institute, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Matthews
authors.affiliation: Bioinformatics and Biostatistics Laboratories, Cancer Research UK London Research Institute, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Kelly
authors.affiliation: Signal Transduction, Cancer Research UK London Research Institute, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Jordan
authors.affiliation: Signal Transduction, Cancer Research UK London Research Institute, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Castellano
authors.affiliation: Signal Transduction, Cancer Research UK London Research Institute, London, UK.|The Institute of Cancer Research, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Downward
mesh_terms: D000072283:A549 Cells; D000818:Animals; D023102:Anoikis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D025521:Tumor Suppressor Proteins