Co-overexpression of ELOVL2 and ELOVL5 promotes clear cell renal cell carcinoma progression through LIMK1-mediated cytoskeletal reorganization.

Clear cell renal cell carcinoma (ccRCC) frequently exhibits dysregulated lipid metabolism yet the contribution of polyunsaturated fatty acid (PUFA) elongation to malignant phenotypes remains incompletely defined. Because PUFA-elongation enzymes ELOVL2 and ELOVL5 are highly expressed in ccRCC, we investigated the clinical and functional significance of their co-overexpression. Using TCGA-KIRC data and clinical ccRCC specimens, we assessed ELOVL2/ELOVL5 expression and associations with clinicopathological features and survival. Functional studies using siRNA-mediated knockdown in renal cancer cell lines demonstrated that dual knockdown markedly suppressed proliferation, invasion, and invadopodia formation. Transcriptomic profiling and pathway analyses indicated that dual knockdown downregulated actin filament-related processes and identified LIMK1 as a candidate mediator. LIMK1 knockdown phenocopied the effects on proliferation, invasion, and invadopodia. These findings link PUFA-elongation programs to LIMK1-associated cytoskeletal remodeling in ccRCC and suggest that the ELOVL2/ELOVL5-LIMK1 axis may represent a therapeutic vulnerability.