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2015 ; 1
(7
): e131
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LIF is a new p53 negative regulator
#MMPMID26161442
Liu J
; Yu H
; Hu W
J Nat Sci
2015[]; 1
(7
): e131
PMID26161442
show ga
Leukemia inhibitory factor (LIF), a cytokine that belongs to the interleukin-6
family, regulates multiple important biological functions. Recently, we found
that LIF is an important negative regulator of p53 in human colorectal cancer
cells. LIF negatively regulates p53 protein levels and functions by activation of
the Stat3 signaling pathway, which in turn induces the expression of ID1, the
helix-loop-helix (HLH) protein inhibitor of differentiation and DNA binding. ID1
increases MDM2 expression at both mRNA and protein levels to accelerate p53
protein degradation. Overexpression of LIF increases chemoresistance of cultured
colorectal cancer cells and colorectal xenograft tumors in a largely
p53-dependent manner. Furthermore, LIF is overexpressed in a large percentage of
human colorectal cancer specimens and LIF overexpression is associated with a
poor prognosis in colorectal cancer patients. Our study revealed a new role of
LIF in tumorigenesis through regulation of the p53 signaling pathway.