ABCC3 is a novel target for the treatment of pancreatic cancer

Publication date: Available online 24 April 2019Source: Advances in Biological RegulationAuthor(s): 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 FalascaAbstractPancreatic 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 to 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 or pharmacological inhibition reduces pancreatic cancer cell growth in vitro and in vivo. Mechanistica...
Source: Advances in Biological Regulation - Category: Biology Source Type: research