Notes

MT1-MMP reliant repression of the tumor suppressor SPRY4 plays a part in MT1-MMP powered melanoma cellular mobility.
Together our findings demonstrate that CBFβ can determine the plasticity of the metastatic cancer cell phenotype, suggesting that its regulation in different micro-environments may play a key role in the establishment of metastatic tumours.C1GALT1 controls the crucial step of GalNAc-type O-glycosylation and is associated with both physiologic and pathologic conditions, including cancers. EPH receptors comprise the largest family of receptor tyrosine kinases (RTKs) and modulate a diverse range of developmental processes and human diseases. However, the role of C1GALT1 in the signaling of EPH receptors remains largely overlooked. Here, we showed that C1GALT1 high expression in gastric adenocarcinomas correlated with adverse clinicopathologic features and is an independent prognostic factor for poor overall survival. Silencing or loss of C1GALT1 inhibited cell viability, migration, invasion, tumor growth and metastasis, as well as increased apoptosis and cytotoxicity of 5-fluorouracil in AGS and MKN45 cells. Phospho-RTK array and western blot analysis showed that C1GALT1 depletion suppressed tyrosine phosphorylation of EPHA2 induced by soluble Ephrin A1-Fc. O-glycans on EPHA2 were modified by C1GALT1 and both S277A and T429A mutants, which are O-glycosites on EPHA2, dramatically enhanced phosphorylation of Y588, suggesting that not only overall O-glycan structures but also site-specific O-glycosylation can regulate EPHA2 activity. Furthermore, depletion of C1GALT1 decreased Ephrin A1-Fc induced migration and reduced Ephrin A1 binding to cell surfaces. The effects of C1GALT1 knockdown or knockout on cell invasiveness in vitro and in vivo were phenocopied by EPHA2 knockdown in gastric cancer cells. These results suggest that C1GALT1 promotes phosphorylation of EPHA2 and enhances soluble Ephrin A1-mediated migration primarily by modifying EPHA2 O-glycosylation. Our study highlights the importance of GalNAc-type O-glycosylation in EPH receptor-regulated diseases and identifies C1GALT1 as a potential therapeutic target for gastric cancer.Thyroid cancer is the fastest growing cancer among all solid tumors in recent decades. Papillary thyroid carcinoma (PTC) is the most predominant type of thyroid cancer. Around 30% of PTC patients with distant metastases and local invasion receive poor prognosis. Thus, the identification of new druggable biological targets is of great importance. Accumulating evidence indicates that solute carrier family numbers have emerged as obligate effectors during the progression of multiple malignancies. Here, we uncovered the functional significance, molecular mechanisms, and clinical impact of solute carrier family 34 member A2 (SLC34A2) in PTC. SLC34A2 was markedly overexpressed in PTC tissues at both mRNA and protein levels compared with matched adjacent normal tissues due to promoter hypomethylation mediated by the DNA methyltransferase 3 beta (DNMT3B). Furthermore, a series of in vivo and in vitro gain- or loss-of-functional assays elucidated the role of SLC34A2 in boosting cell proliferation, cell cycle progression, migration, invasion, and adhesion of PTC cells. Using immunoprecipitation and mass spectrometry, we discovered that SLC34A2 bound to the actin-binding repeats domain of Cortactin (CTTN), thereby inducing the invadopodia formation of PTC cells to promote the metastasis potential of PTC cells. Besides, our mechanistic studies, as well as gene set enrichment analysis (GSEA), have pinpointed the PTEN/AKT/FOXO3a pathway as a major signaling functioning downstream of SLC34A2 regulated cell growth. Taken together, our results highlighted that SLC34A2 plays a pivotal oncogenic role during carcinogenesis and metastasis through distinct mechanisms in PTC.Mitochondrial fusion and fission dynamics fine-tune cellular calcium homeostasis, ATP production capacity and ROS production and play important roles in cell proliferation and migration. Dysregulated mitochondrial dynamics is closely related to tumor development, but the mechanism of mitochondrial dynamics dysregulation and its role in the development of lung cancer remains unclear. Here, we demonstrate that the DNA sensor protein absent in melanoma 2 (AIM2) is highly expressed in non-small cell lung cancer (NSCLC) cells and that high AIM2 expression is associated with poor prognosis in patients with NSCLC. High expression of AIM2 contributes to tumor cell growth and proliferation independent of inflammasome activation in vitro and in vivo. Further studies have shown that AIM2 colocalizes with mitochondria in NSCLC cells and that AIM2 knockdown leads to enhanced mitochondrial fusion and decreased cell proliferation. Mechanistic studies have shown that AIM2 downregulation promotes MFN2 upregulation, thereby enhancing mitochondrial fusion. Moreover, we found that mitochondrial fusion driven by AIM2 knockdown leads to a decrease of cellular reactive oxygen species (ROS) production, which further causes inactivation of the MAPK/ERK signaling pathway. Together, we discovered a novel function of AIM2 in promoting NSCLC development by regulating mitochondrial dynamics and revealed its underlying mechanism. Our work provides new intervention targets for the treatment of NSCLC.We designed this study to assess if surgical safety can be improved by intraoperative use of intraocular lens (IOL) for cataract phacoemulsification. We performed phacoemulsification cataract removal on 401 patients. SecinH3 mouse We randomly assigned these patients into three groups the standard setting (Group I, n = 134), with reduced vacuum and flow rate (Group II, n = 137), and with IOL insertion before the last quadrant was emulsified with standard setting (Group III, n = 130). The primary outcomes included the risk of posterior capsular rupture (PCR), ultrasound time, energy, and complications. The secondary outcomes included central corneal thickness (CCT), CCT changes, endothelial cells (ETC) counting, ETC loss, and the best corrected distance visual acuity (BCVA) measured on day 1, day 7 and day 30. If PCR occurred, we emulsified the residual lens materials after insertion of IOL and clean of the prolapsed vitreous. We found that the risk of PCR in Group III (0/130) was lower than Group I (9/134, corrected relative risk (RR) = 18.
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