CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer.
The CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete. Here, we analyze genetic interactions between mutations of CBFB...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009553 |
| _version_ | 1818736039511982080 |
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| author | Navdeep Malik Hualong Yan Howard H Yang Gamze Ayaz Wendy DuBois Yu-Chou Tseng Young-Im Kim Shunlin Jiang Chengyu Liu Maxwell Lee Jing Huang |
| author_facet | Navdeep Malik Hualong Yan Howard H Yang Gamze Ayaz Wendy DuBois Yu-Chou Tseng Young-Im Kim Shunlin Jiang Chengyu Liu Maxwell Lee Jing Huang |
| author_sort | Navdeep Malik |
| collection | DOAJ |
| description | The CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete. Here, we analyze genetic interactions between mutations of CBFB and other highly mutated genes in human breast cancer datasets and find that CBFB and TP53 mutations are mutually exclusive, suggesting a functional association between CBFB and p53. Integrated genomic studies reveal that TAp73 is a common transcriptional target of CBFB and p53. CBFB cooperates with p53 to maintain TAp73 expression, as either CBFB or p53 loss leads to TAp73 depletion. TAp73 re-expression abrogates the tumorigenic effect of CBFB deletion. Although TAp73 loss alone is insufficient for tumorigenesis, it enhances the tumorigenic effect of NOTCH3 overexpression, a downstream event of CBFB loss. Immunohistochemistry shows that p73 loss is coupled with higher proliferation in xenografts. Moreover, TAp73 loss-of-expression is a frequent event in human breast cancer tumors and cell lines. Together, our results significantly advance our understanding of the tumor suppressive functions of CBFB and reveal a mechanism underlying the communication between the two tumor suppressors CBFB and p53. |
| first_indexed | 2024-12-18T00:30:49Z |
| format | Article |
| id | doaj.art-bd92132d66e74b4e8fce16a33bde98e7 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-18T00:30:49Z |
| publishDate | 2021-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-bd92132d66e74b4e8fce16a33bde98e72022-12-21T21:27:09ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-05-01175e100955310.1371/journal.pgen.1009553CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer.Navdeep MalikHualong YanHoward H YangGamze AyazWendy DuBoisYu-Chou TsengYoung-Im KimShunlin JiangChengyu LiuMaxwell LeeJing HuangThe CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete. Here, we analyze genetic interactions between mutations of CBFB and other highly mutated genes in human breast cancer datasets and find that CBFB and TP53 mutations are mutually exclusive, suggesting a functional association between CBFB and p53. Integrated genomic studies reveal that TAp73 is a common transcriptional target of CBFB and p53. CBFB cooperates with p53 to maintain TAp73 expression, as either CBFB or p53 loss leads to TAp73 depletion. TAp73 re-expression abrogates the tumorigenic effect of CBFB deletion. Although TAp73 loss alone is insufficient for tumorigenesis, it enhances the tumorigenic effect of NOTCH3 overexpression, a downstream event of CBFB loss. Immunohistochemistry shows that p73 loss is coupled with higher proliferation in xenografts. Moreover, TAp73 loss-of-expression is a frequent event in human breast cancer tumors and cell lines. Together, our results significantly advance our understanding of the tumor suppressive functions of CBFB and reveal a mechanism underlying the communication between the two tumor suppressors CBFB and p53.https://doi.org/10.1371/journal.pgen.1009553 |
| spellingShingle | Navdeep Malik Hualong Yan Howard H Yang Gamze Ayaz Wendy DuBois Yu-Chou Tseng Young-Im Kim Shunlin Jiang Chengyu Liu Maxwell Lee Jing Huang CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer. PLoS Genetics |
| title | CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer. |
| title_full | CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer. |
| title_fullStr | CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer. |
| title_full_unstemmed | CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer. |
| title_short | CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer. |
| title_sort | cbfb cooperates with p53 to maintain tap73 expression and suppress breast cancer |
| url | https://doi.org/10.1371/journal.pgen.1009553 |
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