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      Loss of profilin 2 contributes to enhanced epithelial-mesenchymal transition and metastasis of colorectal cancer

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          Abstract

          Profilin 2 (PFN2) functions as an actin cytoskeleton regulator and serves an important role in cell motility. However, a role for PFN2 in the progression of colorectal cancer (CRC), particularly in metastasis, has yet to be clarified. The aim of the present study was to investigate whether PFN2 served specific roles in the progression of human CRC. The results demonstrated that PFN2 was differentially expressed in CRC tissues and cell lines by reverse transcription-quantitative polymerase chain reaction and western blotting. PFN2 expression was also negatively associated with the degree of tumor metastasis. Low PFN2 expression in CRC cells was related with enhanced epithelial-mesenchymal transition (EMT) and, in turn, may increase migratory capabilities. Overexpression of PFN2 in CRC cell lines with a low level of endogenous PFN2 inhibited the EMT process, as well as the associated migration; in addition, myosin light chain (MLC) phosphorylation was upregulated. Inhibition of MLC phosphorylation attenuated the inhibition of EMT and cell migratory abilities induced by PFN2 overexpression in CRC cell lines, the results suggested that PFN2 may suppress cancer EMT and the subsequent metastasis by regulating cytoskeletal reorganization. These results demonstrated that PFN2 may serve a suppressive role in the metastasis of CRC and therefore may provide a new potential target for cancer therapeutics.

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          Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation.

          Transplantation of in-vitro-generated organ buds is a promising approach toward regenerating functional and vascularized organs. Though it has been recently shown in the context of liver models, demonstrating the applicability of this approach to other systems by delineating the molecular mechanisms guiding organ bud formation is critical. Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine.
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            Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP.

            Cells sustain high rates of actin filament elongation by maintaining a large pool of actin monomers above the critical concentration for polymerization. Profilin-actin complexes constitute the largest fraction of polymerization-competent actin monomers. Filament elongation factors such as Ena/VASP and formin catalyze the transition of profilin-actin from the cellular pool onto the barbed end of growing filaments. The molecular bases of this process are poorly understood. Here we present structural and energetic evidence for two consecutive steps of the elongation mechanism: the recruitment of profilin-actin by the last poly-Pro segment of vasodilator-stimulated phosphoprotein (VASP) and the binding of profilin-actin simultaneously to this poly-Pro and to the G-actin-binding (GAB) domain of VASP. The actin monomer bound at the GAB domain is proposed to be in position to join the barbed end of the growing filament concurrently with the release of profilin.
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              Impact of the Preoperative Controlling Nutritional Status (CONUT) Score on the Survival after Curative Surgery for Colorectal Cancer

              Background Recently, the preoperative immune-nutritional status has been reported to correlate with the survival rate in patients with colorectal cancer (CRC). However, there have been no reports on the relationship between the controlling nutritional status (CONUT) score and the clinical outcome after curative surgery for CRC. We herein evaluated the prognostic significance of the CONUT score in patients with CRC, and then compared the accuracy of the CONUT score and the prognostic nutritional index (PNI) as a predictor of survival. Methods We retrospectively reviewed a database of 204 patients who underwent curative surgery for Stage II/III CRC. Patients were divided into two groups according to the CONUT score and the PNI. Results The five-year cancer-specific survival (CSS) rate was significantly higher at 92.7% in the low CONUT group, compared to a rate of 81.0% in the high CONUT group (p=0.0016). The five-year CSS was 71.2% in the low PNI group and 92.3% in the high PNI group, which showed a significant difference (p=0.0155). A multivariate analysis showed that lymph node metastasis and the CONUT score were independent risk factors for CSS. Conclusion This study suggested that the CONUT score is a strong independent predictor of the survival among CRC patients.
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                Author and article information

                Journal
                Int J Oncol
                Int. J. Oncol
                IJO
                International Journal of Oncology
                D.A. Spandidos
                1019-6439
                1791-2423
                September 2018
                09 July 2018
                09 July 2018
                : 53
                : 3
                : 1118-1128
                Affiliations
                [1 ]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006
                [2 ]Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai 201800, P. R. China
                Author notes
                Correspondence to: Dr Dechun Li or Dr Songbing He, Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P. R. China, E-mail: sz4304ldc@ 123456sina.com , E-mail: captain_hsb@ 123456163.com
                [*]

                Contributed equally

                Article
                ijo-53-03-1118
                10.3892/ijo.2018.4475
                6065425
                30015842
                68d1ffff-118a-4024-af85-65e4d008e673
                Copyright: © Zhang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 10 November 2017
                : 07 June 2018
                Categories
                Articles

                profilin 2,colorectal cancer,epithelial-mesenchymal transition,migration,myosin light chain

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