ABCC3 is a novel target for the treatment of pancreatic cancer

Aleksandra Adamska, Riccardo Ferro, Rossano Lattanzio, Emily Capone, Alice Domenichini, Verena Damiani, Giovanna Chiorino, Begum Gokcen Akkaya, Kenneth J Linton, Vincenzo De Laurenzi, Gianluca Sala, Marco Falasca

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Pancreatic Ductal Adenocarcinoma (PDAC) is a very aggressive disease, lacking effective therapeutic approaches and leaving PDAC patients with a poor prognosis. The life expectancy of PDAC patients has not experienced a significant change in the last few decades with a five-year survival rate of only 8%. To address this unmet need, novel pharmacological targets must be identified for clinical intervention. ATP Binding Cassette (ABC) transporters are frequently overexpressed in different cancer types and represent one of the major mechanisms responsible for chemoresistance. However, a more direct role for ABC transporters in tumorigenesis has not been widely investigated. Here, we show that ABCC3 (ABC Subfamily C Member 3; previously known as MRP3) is overexpressed in PDAC cell lines and also in clinical samples. We demonstrate that ABCC3 expression is regulated by mutant p53 via miR-34 and that the transporter drives PDAC progression via transport of the bioactive lipid lysophosphatidylinositol (LPI). Disruption of ABCC3 function either by genetic knockdown reduces pancreatic cancer cell growth in vitro and in vivo. Mechanistically, we demonstrate that knockdown of ABCC3 reduce cell proliferation by inhibition of STAT3 and HIF1α signalling pathways, previously been shown to be key regulators of PDAC progression. Collectively, our results identify ABCC3 as a novel and promising target in PDAC therapy.

Originalspråkengelska
Artikelnummer100634
Antal sidor14
TidskriftAdvances in Biological Regulation
Volym73
DOI
StatusPublished - 2019 aug.
Externt publiceradJa

Bibliografisk information

Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi
  • Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Fingeravtryck

Utforska forskningsämnen för ”ABCC3 is a novel target for the treatment of pancreatic cancer”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här