STK35L1 Associates with Nuclear Actin and Regulates Cell Cycle and Migration of Endothelial Cells

BACKGROUND: Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1) phase have the highest potential to migrate. The molecular mechanism linking these two processes is not understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the function of STK35L1, a novel Ser/Thr kinase, localized in the nucleus and nucleolus of endothelial cells. Molecular biological analysis identified a bipartite nuclear localization signal, and nucleolar localization sequences in the N-terminal part of STK35L1. Nuclear actin was identified as a novel binding partner of STK35L1. A class III PDZ binding domains motif was identified in STK35L1 that mediated its interaction with actin. Depletion of STK35L1 by siRNA lead to an accelerated G(1) to S phase transition after serum-stimulation of endothelial cells indicating an inhibitory role of the kinase in G(1) to S phase progression. Cell cycle specific genes array analysis revealed that one gene was prominently downregulated (8.8 fold) in STK35L1 silenced cells: CDKN2A alpha transcript, which codes for p16(INK4a) leading to G(1) arrest by inhibition of CDK4/6. Moreover in endothelial cells seeded on Matrigel, STK35L1 expression was rapidly upregulated, and silencing of STK35L1 drastically inhibited endothelial sprouting that is required for angiogenesis. Furthermore, STK35L1 depletion profoundly impaired endothelial cell migration in two wound healing assays. CONCLUSION/SIGNIFICANCE: The results indicate that by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. The interaction of STK35L1 with nuclear actin might be critical in the regulation of these fundamental endothelial functions

Mucinous cystic neoplasms of the mesentery: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site.</p> <p>Case presentation</p> <p>A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma.</p> <p>Methods and results</p> <p>We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors.</p> <p>Conclusion</p> <p>Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed.</p

Hepatocellular carcinoma-resection or transplant?

Resection and liver transplantation are considered effective treatments for early-stage hepatocellular carcinoma (HCC). As data from randomized trials are lacking, the choice of technique is controversial. Retrospective analyses suggest that for patients with suboptimal liver function, transplantation is the preferred treatment. For patients with preserved liver function and HCC within the Milan criteria, the overall survival rate is similar for both techniques; therefore resection is the preferred treatment. For tumours beyond the Milan criteria but within acceptable expanded criteria, transplantation has a more favourable outcome than resection. As liver grafts are in short supply, resection followed by transplantation once intrahepatic recurrence is detected would spare patients with favourable or very aggressive tumours from transplantation and enable patients with moderately aggressive tumours to undergo timely transplantation. Currently, resection and transplantation are considered complementary in the management of HCC. Expanding the transplantation and resection criteria of HCC needs to be investigated.link_to_subscribed_fulltex