FABP4-mediated ERK phosphorylation promotes renal cancer cell migration.

Abstract

Clear cell Carcinoma (ccRCC) is the most common and lethal subtype among renal cancers. In the present study we investigated the potential role of fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2 on ccRCC progression. Firstly, we found that FABP4 median serum levels were significantly higher in ccRCC patients compared to HD. Based on this result and to evaluate whether FABP4 plays a role on renal cancer malignant phenotype, we analyzed proliferation and migration in 786-O and ACHN cell lines using recombinant FABP4. We found that FABP4 significantly increased cell migration, whereas it had no significant effect on proliferation. As FABP4 is mainly expressed by adipocytes, we measured FABP4 adipocyte conditioned media (Ad-CM) levels showing that Ad-CM from ccRCC (Ad-CM ccRCC) had significantly higher mean values compared to Ad-CM obtained from Healthy Donors (HD). To assess the effects of adipocyte-released FABP-4, on cancer malignant phenotype we evaluated 786-O and ACHN proliferation and migration, using Ad-CM from ccRCC and Ad-CM from HD alone or in combination with FABP4 inhibitor BMS309403. Our results showed that Ad-CM enhanced cell proliferation in ACHN, but not in 786-O and on cell motility in both cell lines and this effect was partially reverted by BMS309403 in both cell lines. Moreover, in both cell lines, FABP4 effect was associated with an increased ERK phosphorylation. Collectively these data support the role of FABP4 in ccRCC progression and its potential use as noninvasive biomarker and therapeutic target for ccRCC.