Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis
Pp. 146-168 (23)
Diab Thoria, Bureau Christophe, Hanoun Naima, Torrisani Jérôme, Vinel Jean-Pierre, Buscail Louis and Cordelier Pierre
Krüppel-like factor (KLF) family members share a three C2H2 zinc finger
DNA binding domain, and are involved in cell proliferation and differentiation control in
normal as in pathological situations. Studies over the past several years support a
significant role for this family of transcription factors in carcinogenesis. KLFs can both
activate and repress genes that participate in cell-cycle regulation. Among them, many
up-regulated genes are inhibitors of proliferation, whereas genes that promote cell
proliferation are repressed. However, several studies do present KLFs as positive
regulator of cell proliferation. KLFs can be deregulated in multiple cancers either by loss
of heterozygosity (LOH), somatic mutation or transcriptional silencing by promoter
hypermethylation. Accordingly, KLF mediates growth inhibition when ectopically
expressed in multiple cancer-derived cell lines through the inhibition of a number of key
oncogenic signalling pathways, and to reverse the tumorogenic phenotype in vivo. Taken
together, these observations suggest that KLFs act as tumor suppressor. However, in
some occasion, KLFs could act as tumor promoters, depending on “cellular context”.
Thus, this review will discuss the roles and the functions of KLF family members in
carcinogenesis, with a special focus on cancers from epithelial origin.
Krüppel-like factors, cell cycle, transcription factor, cancer.
INSERM U1037, CRCT Team 10, 1, avenue Jean Poulhes, BP 84225, 31432 Toulouse Cedex 04, France