Krüppel-like factor 10 (KLF10)

Krüppel-like factor 10 (KLF10), originally identified as TGF-beta-inducible early gene 1 (TIEG1), is a C2H2-type zinc finger transcription factor that functions as a primary mediator of the TGF-beta signaling pathway [NIH, MDPI]. It is ubiquitously expressed and rapidly induced by various stimuli, including TGF-beta, bone morphogenetic proteins, and estrogen, playing a central role in regulating cell proliferation, differentiation, and apoptosis [NIH, Wikipedia]. In the context of oncology, KLF10 typically acts as a tumor suppressor; its downregulation is linked to increased metastasis and poor prognosis in cancers such as pancreatic, breast, and oral carcinoma [MDPI, NIH]. Beyond its role in cancer, KLF10 is a key regulator of metabolic homeostasis and circadian rhythms, particularly in the liver, and it is essential for the development and suppressive function of regulatory T cells (Tregs) [NIH, ACS]. KLF10 also contributes to bone mineralization and cardiac health, with its deficiency linked to osteoporosis and cardiac hypertrophy [NIH]. Although no KLF10-targeted drugs are currently in clinical trials, experimental small-molecule inhibitors like KLF10-IN-1 have been developed to block its DNA-binding activity, suggesting its potential as a therapeutic target for immune-mediated and fibrotic diseases [ACS, MedChemExpress].

Other names

TGF-beta-inducible early gene 1TIEG1TIEGEGR-alphaEGRAKruppel-like factor 10

KLF10 is a DNA-binding transcriptional regulator that recognizes GC-rich Sp1-like sequences (CACCC boxes) in the promoters of target genes [NIH, ACS]. It modulates transcription by recruiting co-repressors such as mSin3A and JARID1B or co-activators to the DNA [NIH]. KLF10 specifically regulates the TGF-beta/SMAD signaling pathway by repressing the inhibitory SMAD7 and activating the stimulatory SMAD2, thereby amplifying TGF-beta-mediated effects on cell growth and apoptosis [NIH, MDPI].