Multidrug resistance protein 4 (MRP4/ABCC4) is overexpressed in clear cell renal cell carcinoma (ccRCC) and is essential to regulate cell proliferation

COLAVITA, JUAN PABLO MELANA; TODARO, JUAN SANTIAGO; DE SOUSA, MAXIMILIANO; MAY, MARÍA; GÓMEZ, NATALIA; YANEFF, AGUSTIN; DI SIERVI, NICOLAS; AGUIRRE, MARÍA VICTORIA; GUIJAS, CARLOS; FERRINI, LEANDRO; DAVIO, CARLOS; RODRÍGUEZ, JUAN PABLO

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ELSEVIER SCIENCE BV

Año: 2020 vol. 161 p. 836 - 847

0141-8130

Kidney cancer accounts for 2.5% of all cancers, with an annual global incidence of almost 300,000 cases leading to111,000 deaths. Approximately 85% of kidney tumors are renal cell carcinoma (RCC) and their major histologicsubtype is clear cell renal cell carcinoma (ccRCC). Although new therapeutic treatments are being designedand applied based on the combination of tyrosine kinase inhibitors and immunotherapy, no major impact onthe mortality has been reported so far.MRP4 is a pump efflux that transporters multiple endogenous and exogenous substances. Recently it has beenassociated with tumoral persistence and cell proliferation in several types of cancer including pancreas, lung,ovary, colon, ostesarcoma, etc.Herein, we demonstrate for the first time, that MRP4 is overexpressed in ccRCC tumors, compared to controlrenal tissues. In addition, using cell culture models, we observed thatMRP4 pharmacological inhibition producesan imbalance in cAMPmetabolism, induces cell arrest, changes in lipid composition, increase in cytoplasmic lipiddroplets and finally apoptosis.These data provide solid evidence for the future evaluation ofMRP4 as a possible newtherapeutic target in ccRCC.