Tumour-suppression function of KLF12 through regulation of anoikis.
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Date
2016-06ICR Author
Author
Godin-Heymann, N
Brabetz, S
Murillo, MM
Saponaro, M
Santos, CR
Lobley, A
East, P
Chakravarty, P
Matthews, N
Kelly, G
Jordan, S
Castellano, E
Downward, J
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Cell Line, Tumor
Animals
Mice, Inbred NOD
Mice, Knockout
Humans
Mice, SCID
Lung Neoplasms
Neoplasm Metastasis
Tumor Suppressor Proteins
Transplantation, Heterologous
Flow Cytometry
Survival Analysis
Reverse Transcriptase Polymerase Chain Reaction
Cell Cycle
Anoikis
Cell Proliferation
Down-Regulation
Gene Expression Regulation, Neoplastic
RNA Interference
Kruppel-Like Transcription Factors
A549 Cells
Research team
Lung Cancer Group
Language
eng
Date accepted
2015-09-05
License start date
2016-06
Citation
Oncogene, 2016, 35 (25), pp. 3324 - 3334