RRC ID 62773
Author Mori J, Tanikawa C, Funauchi Y, Lo PH, Nakamura Y, Matsuda K.
Title Cystatin C as a p53-inducible apoptotic mediator that regulates cathepsin L activity.
Journal Cancer Sci
Abstract In response to various cellular stresses, p53 is activated and inhibits malignant transformation through the transcriptional regulation of its target genes. However, the full picture of the p53 downstream pathway still remains to be elucidated. Here we identified cystatin C, a major inhibitor of cathepsins, as a novel p53 target. In response to DNA damage, activated p53 induced cystatin C expression through p53 binding sequence in the first intron. We showed that cathepsin L activity was decreased in HCT116 p53(+/+) cells after adriamycin treatment, but not in HCT116 p53(-/-) cells. We also found that knockdown of cystatin C reduced adriamycin-induced caspase-3 activation. Cystatin C expression was significantly downregulated in breast cancer cells with p53 mutations, and decreased cystatin C expression was associated with poor prognosis of breast cancer. Our findings revealed an important role of the p53-cystatin C pathway in human carcinogenesis.
Volume 107(3)
Pages 298-306
Published 2016-3-1
DOI 10.1111/cas.12881
PMID 26757339
PMC PMC4814261
MeSH Adenocarcinoma / genetics Adenocarcinoma / metabolism* Adenocarcinoma / mortality Apoptosis Base Sequence Binding Sites Breast Neoplasms / genetics Breast Neoplasms / metabolism Breast Neoplasms / mortality Cathepsin L / metabolism* Colorectal Neoplasms / genetics Colorectal Neoplasms / metabolism Colorectal Neoplasms / mortality Consensus Sequence Cystatin C / physiology* DNA Damage Female Gene Expression Regulation, Neoplastic HCT116 Cells HEK293 Cells Humans Male Middle Aged Mutation Proportional Hazards Models Transcriptional Activation Tumor Suppressor Protein p53 / physiology*
IF 4.966
Resource
Human and Animal Cells 293T(RCB2202)