MTFR2 Promotes the Proliferation, Migration, and Invasion of Oral Squamous Carcinoma by Switching OXPHOS to Glycolysis.

MTFR2 is an oncogene involved in the progression of cancer, its' potential mechanism in oral squamous carcinoma remains unknown. The aim of this study was to uncover the bio-function and the mechanism of MTFR2 in the progression of oral squamous carcinoma. We scanned TCGA database to identify MTFR2 as dysregulated genes. qRT-PCR and Western blotting assays were applied to detect the expression pattern of MTFR2 in oral squamous carcinoma. We next established stable MTFR2-overexpressing and MTFR2 knocking down cell lines. A series of experiments were applied and the results indicated that MTFR2 was upregulated in cancer tissue and negatively correlated with the overall survival (OS) of patients in both the TCGA database and our inhouse database. Following experiments showed that MTFR2 promotes proliferation, migration and invasion in an oral squamous carcinoma cell line by switching OXPHOS to glycolysis.

No evidence for ß cell neogenesis in murine adult pancreas.

Whether facultative ß cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. To track ß cell neogenesis in vivo, we generated transgenic mice that transiently coexpress mTomato and GFP in a time-sensitive, nonconditional Cre-mediated manner, so that insulin-producing cells express GFP under control of the insulin promoter, while all other cells express mTomato (INSCremTmG mice). Newly differentiated ß cells were detected by flow cytometry and fluorescence microscopy, taking advantage of their transient coexpression of GFP and mTomato fluorescent proteins. We found that ß cell neogenesis predominantly occurs during embryogenesis, decreases dramatically shortly after birth, and is completely absent in adults across various models of ß cell loss, ß cell growth and regeneration, and inflammation. Moreover, we demonstrated upregulation of neurogenin 3 (NGN3) in both proliferating ducts and preexisting ß cells in the ligated pancreatic tail after pancreatic ductal ligation. These results are consistent with some recent reports, but argue against the widely held belief that NGN3 marks cells undergoing endocrine neogenesis in the pancreas. Our data suggest that ß cell neogenesis in the adult pancreas occurs rarely, if ever, under either normal or pathological conditions.

Hypoglycemia reduces vascular endothelial growth factor A production by pancreatic beta cells as a regulator of beta cell mass.

VEGF-A expression in beta cells is critical for pancreatic development, formation of islet-specific vasculature, and Insulin secretion. However, two key questions remain. First, is VEGF-A release from beta cells coupled to VEGF-A production in beta cells? Second, how is the VEGF-A response by beta cells affected by metabolic signals? Here, we show that VEGF-A secretion, but not gene transcription, in either cultured islets or purified pancreatic beta cells, was significantly reduced early on during low glucose conditions. In vivo, a sustained hypoglycemia in mice was induced with Insulin pellets, resulting in a significant reduction in beta cell mass. This loss of beta cell mass could be significantly rescued with continuous delivery of exogenous VEGF-A, which had no effect on beta cell mass in normoglycemic mice. In addition, an increase in apoptotic endothelial cells during hypoglycemia preceded an increase in apoptotic beta cells. Both endothelial and beta cell apoptosis were prevented by exogenous VEGF-A, suggesting a possible causative relationship between reduced VEGF-A and the loss of islet vasculature and beta cells. Furthermore, in none of these experimental groups did beta cell proliferation and islet vessel density change, suggesting a tightly regulated balance between these two cellular compartments. The average islet size decreased in hypoglycemia, which was also prevented by exogenous VEGF-A. Taken together, our data suggest that VEGF-A release in beta cells is independent of VEGF-A synthesis. Beta cell mass can be regulated through modulated release of VEGF-A from beta cells based on physiological need.