Cofilin (CFL) is an F-actin–severing protein required for the cytoskeleton reorganization and filopodia formation, which drives cell migration. CFL binding and severing of F-actin is controlled by Ser3 phosphorylation, but the contributions of this step to cell migration during invasion and metastasis of cancer cells are unclear. In this study, we addressed the question in prostate cancer cells, including the response to TGF-β, a critical regulator of migration. In cells expressing wild-type CFL, TGF-β treatment increased LIMK-2 activity and cofilin phosphorylation, decreasing filopodia formation. Conversely, constitutively active CFL (SerAla) promoted filipodia formation and cell migration mediated by TGF-β. Notably, in cocultures of prostate cancer epithelial cells and cancer-associated fibroblasts, active CFL promoted invasive migration in response to TGF-β in the microenvironment. Further, constitutively active CFL elevated the metastatic ability of prostate cancer cells in vivo. We found that levels of active CFL correlated with metastasis in a mouse model of prostate tumor and that in human prostate cancer, CFL expression was increased significantly in metastatic tumors. Our findings show that the actin-severing protein CFL coordinates responses to TGF-β that are needed for invasive cancer migration and metastasis.

Background In patients seen in the emergency department (ED) with acute stone obstruction many risk factors that indicate need for urgent renal drainage are known. However, in patients discharged from ED without renal drainage factors that can minimize revisit to the emergency department are not fully identified. We evaluated SIRS (systemic inflammatory response syndrome) as a risk factor for urgent renal drainage and revisit to the ED in patients with acute stone colic during their ED visit. Methods Retrospective review was performed of patients presenting to a tertiary academic emergency department (ED) from an obstructing ureteral or UPJ stone with hydronephrosis confirmed on an abdominal and pelvic CT scan. Data evaluated over a 3-year period included stone size, presence of UTI, presence or absence of SIRS and other clinical variables as risk factors for urgent renal drainage and ED revisits. Results 1983 patients with urolithiasis were seen at the ED and 649 patients had obstructive urolithiasis on CT scan. SIRS was diagnosed in 15% (99/649) patients. 54/99 (55%) patients with SIRS underwent urgent renal drainage compared to 99/550 (17%) in non-SIRS patients. In a multivariate analysis SIRS was a predictor of urgent intervention compared to non-SIRS patients (odds ratio 4.6, p < 0.05). SIRS was also associated with increased risk for revisits to the ED (6.9% with SIRS vs. 2.4% with no SIRS, odds ratio 2.9, p = 0.05). Conclusions Presence of SIRS in obstructive urolithiasis patients was an independent risk factor of acute urologic intervention and revisits to the ED. A timely consultation with a urologist following discharge from ED for obstructive stone patients with SIRS who had no acute renal drainage may prevent revisit to the ED. Evaluation for SIRS in addition to other clinical risk factors should be considered while making management decision in patients with acute stone obstruction.

Urologic tumors continue to represent a huge fraction of cancer cases in the United States, with over 376,310 estimated new diagnoses in 2013. As with many types of tumors, urologic tumors vary greatly in their phenotype, ranging from minimally invasive to malignancies possessing great metastatic potential. The increasing need for more efficient and less invasive methods of cancer detection, as well as the ability to predict severity of the disease phenotype is readily evident—yet reliable methods remain elusive in a clinical setting today. Comprehensive panels of gene clusters are being developed toward the generation of molecular signatures in order to better diagnose urologic malignancies, and identify effective treatment strategies in the emerging era of personalized medicine. In this review, we discuss the current literature on the credibility and biomarker value of such molecular signatures in the context of clinical significance relating to the pathological aggressiveness of urologic tumors (prostate, bladder and renal cancer)—also exploiting their predictive potential in the response to treatment.