PMID:22491752

Citation	Li, J, Zheng, H, Yu, F, Yu, T, Liu, C, Huang, S, Wang, TC and Ai, W (2012) Deficiency of the Kruppel-like factor KLF4 correlates with increased cell proliferation and enhanced skin tumorigenesis. Carcinogenesis 33:1239-46
Abstract	Kruppel-like factor 4 (KLF4) is a transcription factor that is highly expressed in differentiated epithelial cells including that of the skin. It is critical for specification or function of differentiated epithelial cells. Moreover, KLF4 functions either as a tumor suppressor or an oncogene depending on different cellular contexts. However, the role of KLF4 in skin tumorigenesis remains controversial. To address this issue, we first examined KLF4 expression using a cohort of samples from patients with skin squamous cell carcinoma and basal cell carcinoma and found that in 21 of 24 tumor tissues (87.5%), KLF4 expression as assayed by immunohistochemistry was absent when compared with that in normal tissues. In addition, knockdown of KLF4 in human epidermal squamous cell carcinoma SCC13 cells was accompanied by increased cell growth. Further analysis revealed that KLF4 deficiency promoted cell migration and adhesion, which are the important properties of tumor cells. These observations were supported by the effect upon overexpression of KLF4 in SCC13 cells. Furthermore, we generated a novel tamoxifen-inducible KLF4/CreER and KLF4(flox) double transgenic mouse model to examine the role of KLF4 in skin cancer development. Consistent with in vitro studies, KLF4 deficiency increased the ability of migration and adhesion of mouse primary skin keratinocytes. Moreover, KLF4 knockout led to increased cell proliferation and skin carcinogenesis in a classical DMBA/TPA mouse skin cancer model. Taken together, our data suggest that KLF4 inhibits cell proliferation, migration and adhesion and that loss of KLF4 promotes skin tumorigenesis.
Links	PubMed PMC3388492 Online version:10.1093/carcin/bgs143
Keywords	9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Basal Cell/genetics; Carcinoma, Basal Cell/metabolism; Carcinoma, Basal Cell/pathology; Carcinoma, Squamous Cell/genetics; Carcinoma, Squamous Cell/metabolism; Carcinoma, Squamous Cell/pathology; Cell Adhesion/genetics; Cell Differentiation; Cell Movement/genetics; Cell Proliferation; Cell Transformation, Neoplastic; Cells, Cultured; Female; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes/metabolism; Kruppel-Like Transcription Factors/deficiency; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Mice; Mice, Transgenic; RNA Interference; RNA, Small Interfering; Skin Neoplasms/chemically induced; Skin Neoplasms/metabolism; Skin Neoplasms/pathology; Tamoxifen/pharmacology; Tetradecanoylphorbol Acetate
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:KLF4	involved_in	GO:0030336: negative regulation of cell migration	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:KLF4		GO:0030336: negative regulation of cell migration	ECO:0000315:		P		Figure 4 shows that knock-out of the KLF4 gene results in increased cell migration.	complete CACAO 4861

References

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