Cargando…
Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer
Emerging evidence demonstrates that RUNX3 is a tumor suppressor in breast cancer. Inactivation of RUNX3 in mice results in spontaneous mammary gland tumors, and decreased or silenced expression of RUNX3 is frequently found in breast cancer cell lines and human breast cancer samples. However, the und...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438320/ https://www.ncbi.nlm.nih.gov/pubmed/22580604 http://dx.doi.org/10.1038/onc.2012.178 |
_version_ | 1782242901331279872 |
---|---|
author | Tsang, Ying-Hung Nicole Wu, Xue-Wei Lim, Jing-Shan Ong, Chee Wee Salto-Tellez, Manuel Ito, Kosei Ito, Yoshiaki Chen, Lin-Feng |
author_facet | Tsang, Ying-Hung Nicole Wu, Xue-Wei Lim, Jing-Shan Ong, Chee Wee Salto-Tellez, Manuel Ito, Kosei Ito, Yoshiaki Chen, Lin-Feng |
author_sort | Tsang, Ying-Hung Nicole |
collection | PubMed |
description | Emerging evidence demonstrates that RUNX3 is a tumor suppressor in breast cancer. Inactivation of RUNX3 in mice results in spontaneous mammary gland tumors, and decreased or silenced expression of RUNX3 is frequently found in breast cancer cell lines and human breast cancer samples. However, the underlying mechanism for initiating RUNX3 inactivation in breast cancer remains elusive. Here, we identify prolyl-isomerase Pin1, which is often over-expressed in breast cancer, as a key regulator of RUNX3 inactivation. In human breast cancer cell lines and breast cancer samples, expression of Pin1 inversely correlates with the expression of RUNX3. In addition, Pin1 recognizes four phosphorylated Ser/Thr-Pro motifs in RUNX3 via its WW domain. Binding of Pin1 to RUNX3 suppresses the transcriptional activity of RUNX3. Furthermore, Pin1 reduces the cellular levels of RUNX3 in an isomerase activity-dependent manner by inducing the ubiquitination and proteasomal degradation of RUNX3. Knocking down Pin1 enhances the cellular levels and transcriptional activity of RUNX3 by inhibiting the ubiquitination and degradation of RUNX3. Our results identify Pin1 as a new regulator of RUNX3 inactivation in breast cancer. |
format | Online Article Text |
id | pubmed-3438320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-34383202013-09-21 Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer Tsang, Ying-Hung Nicole Wu, Xue-Wei Lim, Jing-Shan Ong, Chee Wee Salto-Tellez, Manuel Ito, Kosei Ito, Yoshiaki Chen, Lin-Feng Oncogene Article Emerging evidence demonstrates that RUNX3 is a tumor suppressor in breast cancer. Inactivation of RUNX3 in mice results in spontaneous mammary gland tumors, and decreased or silenced expression of RUNX3 is frequently found in breast cancer cell lines and human breast cancer samples. However, the underlying mechanism for initiating RUNX3 inactivation in breast cancer remains elusive. Here, we identify prolyl-isomerase Pin1, which is often over-expressed in breast cancer, as a key regulator of RUNX3 inactivation. In human breast cancer cell lines and breast cancer samples, expression of Pin1 inversely correlates with the expression of RUNX3. In addition, Pin1 recognizes four phosphorylated Ser/Thr-Pro motifs in RUNX3 via its WW domain. Binding of Pin1 to RUNX3 suppresses the transcriptional activity of RUNX3. Furthermore, Pin1 reduces the cellular levels of RUNX3 in an isomerase activity-dependent manner by inducing the ubiquitination and proteasomal degradation of RUNX3. Knocking down Pin1 enhances the cellular levels and transcriptional activity of RUNX3 by inhibiting the ubiquitination and degradation of RUNX3. Our results identify Pin1 as a new regulator of RUNX3 inactivation in breast cancer. 2012-05-14 2013-03-21 /pmc/articles/PMC3438320/ /pubmed/22580604 http://dx.doi.org/10.1038/onc.2012.178 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Tsang, Ying-Hung Nicole Wu, Xue-Wei Lim, Jing-Shan Ong, Chee Wee Salto-Tellez, Manuel Ito, Kosei Ito, Yoshiaki Chen, Lin-Feng Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer |
title | Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer |
title_full | Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer |
title_fullStr | Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer |
title_full_unstemmed | Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer |
title_short | Prolyl isomerase Pin1 down-regulates tumor suppressor RUNX3 in breast cancer |
title_sort | prolyl isomerase pin1 down-regulates tumor suppressor runx3 in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438320/ https://www.ncbi.nlm.nih.gov/pubmed/22580604 http://dx.doi.org/10.1038/onc.2012.178 |
work_keys_str_mv | AT tsangyinghungnicole prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT wuxuewei prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT limjingshan prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT ongcheewee prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT saltotellezmanuel prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT itokosei prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT itoyoshiaki prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer AT chenlinfeng prolylisomerasepin1downregulatestumorsuppressorrunx3inbreastcancer |