PMID- 33167919
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20210510
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 20
IP  - 1
DP  - 2020 Nov 10
TI  - EP300 knockdown reduces cancer stem cell phenotype, tumor growth and metastasis 
      in triple negative breast cancer.
PG  - 1076
LID - 10.1186/s12885-020-07573-y [doi]
LID - 1076
AB  - BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive breast cancer 
      subtype with basal features, lacking the expression of receptors targeted 
      successfully in other breast cancer subtypes. Treatment response to adjuvant and 
      neoadjuvant chemotherapy is often short-lived and metastatic spread occurs at 
      higher rates than other subtypes within the first five years after diagnosis. 
      TNBCs exhibit stem cell features and are enriched for cancer stem cell (CSC) 
      populations. E1A Binding Protein P300 (EP300) is a large protein with multiple 
      cellular functions, including as an effector in stem cell biology. METHODS: We 
      used a genetic knockdown (KD) model of EP300 in TNBC cell lines to investigate 
      the effect on CSC phenotype, tumor growth and metastasis. Side population assay 
      and tumorsphere suspension culture were used in vitro. Xenograft mouse models 
      were used for in vivo studies. We performed in silico analysis of publicly 
      available gene expression data sets to investigate CSC gene expression and 
      molecular pathways as well as survival outcomes associated with EP300 expression 
      in patients with TNBC and basal-like BC. RESULTS: EP300 KD abolished the CSC 
      phenotype by reducing ABCG2 expression, side population cells and tumorsphere 
      formation capacity in vitro as well as tumor formation in a xenograft mouse model 
      in vivo. Metastatic capacity was markedly reduced in EP300 KD cells in vivo, with 
      no detection of circulating tumor cells. TCGA data analysis demonstrated that 
      genes positively correlated with EP300 expression in TNBC and basal-like BC were 
      associated with CSC biology. Survival analysis demonstrated that EP300 expression 
      predicts poor recurrence free survival in TNBC and basal BC. CONCLUSION: We 
      report a novel oncogenic role for EP300 in driving CSC phenotype representing a 
      potential target to address tumor initiation and metastatic spread in TNBC and 
      basal-like BC. EP300 might serve as a prognostic marker and potential therapeutic 
      target in TNBC.
FAU - Ring, Alexander
AU  - Ring A
AUID- ORCID: 0000-0002-0092-1323
AD  - Division of Surgical Oncology, Department of Surgery and University of Southern 
      California Norris Cancer Center, University of Southern California, Los Angeles, 
      CA, USA. alexander.ring@usz.ch.
AD  - Present Address: Department of Medical Oncology and Hematology, 
      Universitatsspital Zurich, Ramistrasse 100, 8091, Zurich, Switzerland. 
      alexander.ring@usz.ch.
FAU - Kaur, Pushpinder
AU  - Kaur P
AD  - Division of Surgical Oncology, Department of Surgery and University of Southern 
      California Norris Cancer Center, University of Southern California, Los Angeles, 
      CA, USA.
FAU - Lang, Julie E
AU  - Lang JE
AD  - Division of Surgical Oncology, Department of Surgery and University of Southern 
      California Norris Cancer Center, University of Southern California, Los Angeles, 
      CA, USA.
LA  - eng
GR  - TG2-01161/California Institute for Regenerative Medicine/
GR  - P30CA014089/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20201110
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (EP300 protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers, Tumor/*metabolism
MH  - Cell Cycle
MH  - Cell Movement
MH  - Cell Proliferation
MH  - E1A-Associated p300 Protein/*antagonists & inhibitors/genetics/metabolism
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lymphatic Metastasis
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplastic Stem Cells/*cytology/metabolism/pathology
MH  - Phenotype
MH  - Triple Negative Breast Neoplasms/metabolism/pathology/*prevention & control
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC7653866
OTO - NOTNLM
OT  - ATP-binding cassette super-family G member 2 (ABCG2)/breast Cancer resistance 
      protein (BCRP)
OT  - Basal-like BC
OT  - Cancer stem cells (CSC)
OT  - E1A-associated protein p300 (EP300)
OT  - Metastasis
OT  - Triple negative breast cancer (TNBC)
COIS- Dr. Julie Lang is on the speaker bureau of Genomic Health and received research 
      funding unrelated to this work from ANGLE Parsortix. All other authors declare no 
      conflict of interest.
EDAT- 2020/11/11 06:00
MHDA- 2021/05/11 06:00
PMCR- 2020/11/10
CRDT- 2020/11/10 05:31
PHST- 2020/04/28 00:00 [received]
PHST- 2020/10/26 00:00 [accepted]
PHST- 2020/11/10 05:31 [entrez]
PHST- 2020/11/11 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2020/11/10 00:00 [pmc-release]
AID - 10.1186/s12885-020-07573-y [pii]
AID - 7573 [pii]
AID - 10.1186/s12885-020-07573-y [doi]
PST - epublish
SO  - BMC Cancer. 2020 Nov 10;20(1):1076. doi: 10.1186/s12885-020-07573-y.