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SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
by
Hunborg, Pamela
, Hsueh, Eddy C.
, Zhang, Yanping
, Wang, Fang
, Rauchman, Michael
, Kiefer, Susan M.
, Ye, Jian
, Robbins, Lynn
, Peng, Guangyong
, Varvares, Mark A.
, Zhong, Xiaoli
, Ma, Chunling
, Si, Fusheng
, Han, Bing
in
Analysis
/ Animals
/ Biomedicine
/ Breast cancer
/ Cancer cells
/ Cancer metastasis
/ Cancer Research
/ Carcinogenesis
/ Care and treatment
/ Cell Line, Tumor
/ Cell Proliferation
/ Cellular Senescence
/ Coculture Techniques
/ Development and progression
/ Down-Regulation
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ MCF-7 Cells
/ Metastasis
/ Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism
/ Mice
/ Neoplasm Metastasis
/ Neoplasm Transplantation
/ NuRD complex
/ Oncology
/ SALL1
/ Senescence
/ Transcription factors
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - metabolism
/ Triple Negative Breast Neoplasms - pathology
/ Tumor suppressor gene
/ Tumorigenesis
2018
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SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
by
Hunborg, Pamela
, Hsueh, Eddy C.
, Zhang, Yanping
, Wang, Fang
, Rauchman, Michael
, Kiefer, Susan M.
, Ye, Jian
, Robbins, Lynn
, Peng, Guangyong
, Varvares, Mark A.
, Zhong, Xiaoli
, Ma, Chunling
, Si, Fusheng
, Han, Bing
in
Analysis
/ Animals
/ Biomedicine
/ Breast cancer
/ Cancer cells
/ Cancer metastasis
/ Cancer Research
/ Carcinogenesis
/ Care and treatment
/ Cell Line, Tumor
/ Cell Proliferation
/ Cellular Senescence
/ Coculture Techniques
/ Development and progression
/ Down-Regulation
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ MCF-7 Cells
/ Metastasis
/ Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism
/ Mice
/ Neoplasm Metastasis
/ Neoplasm Transplantation
/ NuRD complex
/ Oncology
/ SALL1
/ Senescence
/ Transcription factors
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - metabolism
/ Triple Negative Breast Neoplasms - pathology
/ Tumor suppressor gene
/ Tumorigenesis
2018
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SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
by
Hunborg, Pamela
, Hsueh, Eddy C.
, Zhang, Yanping
, Wang, Fang
, Rauchman, Michael
, Kiefer, Susan M.
, Ye, Jian
, Robbins, Lynn
, Peng, Guangyong
, Varvares, Mark A.
, Zhong, Xiaoli
, Ma, Chunling
, Si, Fusheng
, Han, Bing
in
Analysis
/ Animals
/ Biomedicine
/ Breast cancer
/ Cancer cells
/ Cancer metastasis
/ Cancer Research
/ Carcinogenesis
/ Care and treatment
/ Cell Line, Tumor
/ Cell Proliferation
/ Cellular Senescence
/ Coculture Techniques
/ Development and progression
/ Down-Regulation
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ MCF-7 Cells
/ Metastasis
/ Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism
/ Mice
/ Neoplasm Metastasis
/ Neoplasm Transplantation
/ NuRD complex
/ Oncology
/ SALL1
/ Senescence
/ Transcription factors
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - metabolism
/ Triple Negative Breast Neoplasms - pathology
/ Tumor suppressor gene
/ Tumorigenesis
2018
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SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
Journal Article
SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
2018
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Overview
Background
SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.
Methods
We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions.
Results
We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways.
Conclusion
Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Animals
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism
/ Mice
/ Oncology
/ SALL1
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - metabolism
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