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ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription
- Source :
- Cancers, Volume 12, Issue 11, Cancers, Vol 12, Iss 3415, p 3415 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- Breast cancer is a common malignancy, but the understanding of its cellular and molecular mechanisms is limited. ZFHX3, a transcription factor with many homeodomains and zinc fingers, suppresses prostatic carcinogenesis but promotes tumor growth of liver cancer cells. ZFHX3 regulates mammary epithelial cells&rsquo<br />proliferation and differentiation by interacting with estrogen and progesterone receptors, potent breast cancer regulators. However, whether ZFHX3 plays a role in breast carcinogenesis is unknown. Here, we found that ZFHX3 promoted the proliferation and tumor growth of breast cancer cells in culture and nude mice<br />and higher expression of ZFHX3 in human breast cancer specimens was associated with poorer prognosis. The knockdown of ZFHX3 in ZFHX3-high MCF-7 cells decreased, and ZFHX3 overexpression in ZFHX3-low T-47D cells increased the proportion of breast cancer stem cells (BCSCs) defined by mammosphere formation and the expression of CD44, CD24, and/or aldehyde dehydrogenase 1. Among several transcription factors that have been implicated in BCSCs, MYC and TBX3 were transcriptionally activated by ZFHX3 via promoter binding, as demonstrated by luciferase-reporter and ChIP assays. These findings suggest that ZFHX3 promotes breast cancer cells&rsquo<br />proliferation and tumor growth likely by enhancing BCSC features and upregulating MYC, TBX3, and others.
- Subjects :
- 0301 basic medicine
Cancer Research
Estrogen receptor
MYC
Biology
medicine.disease_cause
lcsh:RC254-282
ZFHX3
03 medical and health sciences
0302 clinical medicine
Breast cancer
breast cancer
medicine
cancer cells stemness
skin and connective tissue diseases
Transcription factor
CD24
CD44
TBX3
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Stem cell
Carcinogenesis
Liver cancer
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....709522dfe48d16831792eefd4ccba1c5
- Full Text :
- https://doi.org/10.3390/cancers12113415