SRC-3 inhibition blocks tumor growth of pancreatic ductal adenocarcinoma

Cancer Lett. 2019 Feb 1:442:310-319. doi: 10.1016/j.canlet.2018.11.012. Epub 2018 Nov 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Nude
  • Mice, SCID
  • Neoplasm Invasiveness
  • Nuclear Receptor Coactivator 3 / antagonists & inhibitors*
  • Nuclear Receptor Coactivator 3 / genetics*
  • Nuclear Receptor Coactivator 3 / metabolism
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNAi Therapeutics*
  • Signal Transduction
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • RNA, Small Interfering
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 3