SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma

Xianzhou Song; Hui Chen; Chengwei Zhang; Yang Yu; Zhongyuan Chen; Han Liang; George Van Buren; Amy L. McElhany; William E. Fisher; David M. Lonard; Bert W. O'Malley; Jin Wang

doi:10.1016/j.canlet.2018.11.012

SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma

Xianzhou Song, Hui Chen, Chengwei Zhang, Yang Yu, Zhongyuan Chen, Han Liang, George Van Buren, Amy L. McElhany, William E. Fisher, David M. Lonard, Bert W. O'Malley, Jin Wang

Bioinformatics & Computational Biology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.

Original language	English (US)
Pages (from-to)	310-319
Number of pages	10
Journal	Cancer Letters
Volume	442
DOIs	https://doi.org/10.1016/j.canlet.2018.11.012
State	Published - Feb 1 2019

Keywords

Pancreatic ductal adenocarcinoma
Small molecule inhibitor
Steroid receptor coactivator

ASJC Scopus subject areas

Oncology
Cancer Research

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Advanced Technology Genomics Core
Bioinformatics Shared Resource
Functional Genomics Core
Tissue Biospecimen and Pathology Resource
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10.1016/j.canlet.2018.11.012

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title = "SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.",

keywords = "Pancreatic ductal adenocarcinoma, Small molecule inhibitor, Steroid receptor coactivator",

author = "Xianzhou Song and Hui Chen and Chengwei Zhang and Yang Yu and Zhongyuan Chen and Han Liang and {Van Buren}, George and McElhany, {Amy L.} and Fisher, {William E.} and Lonard, {David M.} and O'Malley, {Bert W.} and Jin Wang",

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year = "2019",

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day = "1",

doi = "10.1016/j.canlet.2018.11.012",

language = "English (US)",

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pages = "310--319",

journal = "Cancer Letters",

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TY - JOUR

T1 - SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma

AU - Song, Xianzhou

AU - Chen, Hui

AU - Zhang, Chengwei

AU - Yu, Yang

AU - Chen, Zhongyuan

AU - Liang, Han

AU - Van Buren, George

AU - McElhany, Amy L.

AU - Fisher, William E.

AU - Lonard, David M.

AU - O'Malley, Bert W.

AU - Wang, Jin

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.

AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal disease with few treatment options. Steroid receptor coactivator-3 (SRC-3, also known as NCOA3, AIB1, pCIP, ACTR, RAC3, TRAM1) sits at the nexus of many growth signaling pathways and has been pursued as a therapeutic target for breast, prostate and lung cancers. In this study, we find that SRC-3 is overexpressed in PDAC and inversely correlates with patient overall survival. Knockdown of SRC-3 reduces pancreatic cancer cell proliferation, migration and invasion in vitro. Additionally, inhibition of SRC-3 using either shRNA or a small molecule inhibitor can significantly inhibit tumor growth in orthotopic pancreatic cancer mouse models. Collectively, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.

KW - Pancreatic ductal adenocarcinoma

KW - Small molecule inhibitor

KW - Steroid receptor coactivator

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EP - 319

JO - Cancer Letters

JF - Cancer Letters

ER -

SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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