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The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53
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Journal Article
The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53
2021
Overview
Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain. PBX3 is involved in the progression of gastric cancer, colorectal cancer, and prostate cancer; however, the detailed mechanism by which it promotes tumor growth remains to be elucidated. Here, we found that
PBX3
silencing induces the expression of the cell cycle regulator p21, leading to an increase in colorectal cancer (CRC) cell apoptosis as well as suppression of proliferation and colony formation. Furthermore, we found that
PBX3
is highly expressed in clinical CRC patients, in whom p21 expression is aberrantly low. We found that the regulation of
p21
transcription by PBX3 occurs through the upstream regulator of
p21
, the tumor suppressor p53, as PBX3 binds to the
p53
promoter and suppresses its transcriptional activity. Finally, we revealed that PBX3 regulates tumor growth through regulation of the p53/p21 axis. Taken together, our results not only describe a novel mechanism regarding PBX3-mediated regulation of tumor growth but also provide new insights into the regulatory mechanism of the tumor suppressor p53.
Publisher
Springer Science and Business Media LLC,Springer Singapore,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Cell Proliferation - physiology
/ Cyclin-dependent kinase inhibitor p21
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humans
/ Male
/ Mice
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Transcription, Genetic - physiology
/ Tumor Suppressor Protein p53
/ Tumor Suppressor Protein p53 - antagonists & inhibitors
/ Tumor Suppressor Protein p53 - genetics
/ Tumor Suppressor Protein p53 - metabolism
/ Tumors
/ Vaccine
