Network Analysis Identifies Regulators of Basal-Like Breast Cancer Reprogramming and Endocrine Therapy Vulnerability.

Szczegóły
Abstrakt

Tytuł:: Network Analysis Identifies Regulators of Basal-Like Breast Cancer Reprogramming and Endocrine Therapy Vulnerability.
Autorzy:: Choi SR; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Hwang CY; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Lee J; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Cho KH; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. .
Źródło:: Cancer research [Cancer Res] 2022 Jan 15; Vol. 82 (2), pp. 320-333. Date of Electronic Publication: 2021 Nov 29.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Baltimore, Md. : American Association for Cancer Research
Original Publication: Chicago [etc.]
MeSH Terms:: Antineoplastic Agents, Hormonal/*therapeutic use
Cellular Reprogramming/*genetics
Cellular Reprogramming Techniques/*methods
Drug Resistance, Neoplasm/*drug effects
Drug Resistance, Neoplasm/*genetics
Tamoxifen/*therapeutic use
Transcriptome/*genetics
Triple Negative Breast Neoplasms/*drug therapy
Triple Negative Breast Neoplasms/*genetics
Antineoplastic Agents, Hormonal/pharmacology ; Cohort Studies ; Estrogen Receptor alpha/antagonists & inhibitors ; Estrogen Receptor alpha/metabolism ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Gene Regulatory Networks ; Histone Deacetylase 1/genetics ; Histone Deacetylase 2/genetics ; Humans ; MCF-7 Cells ; Phenotype ; Repressor Proteins/genetics ; Tamoxifen/pharmacology ; Transfection ; Treatment Outcome ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology
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Substance Nomenclature:: 0 (Antineoplastic Agents, Hormonal)
0 (BCL11A protein, human)
0 (ESR1 protein, human)
0 (Estrogen Receptor alpha)
0 (Repressor Proteins)
094ZI81Y45 (Tamoxifen)
EC 3.5.1.98 (HDAC1 protein, human)
EC 3.5.1.98 (HDAC2 protein, human)
EC 3.5.1.98 (Histone Deacetylase 1)
EC 3.5.1.98 (Histone Deacetylase 2)
Entry Date(s):: Date Created: 20211130 Date Completed: 20220218 Latest Revision: 20220218
Update Code:: 20240104
DOI:: 10.1158/0008-5472.CAN-21-0621
PMID:: 34845001
: Czasopismo naukowe

Basal-like breast cancer is the most aggressive breast cancer subtype with the worst prognosis. Despite its high recurrence rate, chemotherapy is the only treatment for basal-like breast cancer, which lacks expression of hormone receptors. In contrast, luminal A tumors express ERα and can undergo endocrine therapy for treatment. Previous studies have tried to develop effective treatments for basal-like patients using various therapeutics but failed due to the complex and dynamic nature of the disease. In this study, we performed a transcriptomic analysis of patients with breast cancer to construct a simplified but essential molecular regulatory network model. Network control analysis identified potential targets and elucidated the underlying mechanisms of reprogramming basal-like cancer cells into luminal A cells. Inhibition of BCL11A and HDAC1/2 effectively drove basal-like cells to transition to luminal A cells and increased ERα expression, leading to increased tamoxifen sensitivity. High expression of BCL11A and HDAC1/2 correlated with poor prognosis in patients with breast cancer. These findings identify mechanisms regulating breast cancer phenotypes and suggest the potential to reprogram basal-like breast cancer cells to enhance their targetability. SIGNIFICANCE: A network model enables investigation of mechanisms regulating the basal-to-luminal transition in breast cancer, identifying BCL11A and HDAC1/2 as optimal targets that can induce basal-like breast cancer reprogramming and endocrine therapy sensitivity.
(©2021 American Association for Cancer Research.)

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