Overexpressed gene signature of EPH receptor A/B family in cancer patients-comprehensive analyses from the public high-throughput database.

Although a previous study suggested that erythropoietin-producing hepatoma (EPH) receptors play important roles in tumor progression and the overexpression of EPHs in cancer patients is related to poor prognoses, high-throughput gene expression profiling of EPH family members in different types and subtypes of cancers has so far not been conducted. We herein carried out a series of bioinformatic analyses on expressive profiles of every EPH member across 21 different types of clinical cancers versus matched normal tissues gathered from the Oncomine platform. We validated these results by protein expression study of all EPHs family members by The Human Protein Atlas repository. Our results uncovered the overexpression of most EPH subunits in numerous cancer types, especially the dramatic overexpression of six EPHs members, namely EPHA1, EPHA2, EPHA3, EPHA4 and EPHB1, EPHB2, EPHB3, EPHB4 in bladder, colorectal, esophageal, gastric, and prostate cancers. Furthermore, EPHB2 was specifically highly expressed in cervical cancer, EPHA3 in liver cancer, and EPHB1 in uterine cancer. Collectively, expressive profiles of these EPHs were confirmed and correlated with different cancer subtypes as potential biomarkers. This study provides useful information for further studies on cancer development and clinical treatments.

Regulation of islet glucagon secretion: Beyond calcium.

The islet of Langerhans plays a key role in glucose homeostasis through regulated secretion of the hormones insulin and glucagon. Islet research has focused on the insulin-secreting ß-cells, even though aberrant glucagon secretion from α-cells also contributes to the aetiology of diabetes. Despite its importance, the mechanisms controlling glucagon secretion remain controversial. Proper α-cell function requires the islet milieu, where ß- and δ-cells drive and constrain α-cell dynamics. The response of glucagon to glucose is similar between isolated islets and that measured in vivo, so it appears that the glucose dependence requires only islet-intrinsic factors and not input from blood flow or the nervous system. Elevated intracellular free Ca2+ is needed for α-cell exocytosis, but interpreting Ca2+ data is tricky since it is heterogeneous among α-cells at all physiological glucose levels. Total Ca2+ activity in α-cells increases slightly with glucose, so Ca2+ may serve a permissive, rather than regulatory, role in glucagon secretion. On the other hand, cAMP is a more promising candidate for controlling glucagon secretion and is itself driven by paracrine signalling from ß- and δ-cells. Another pathway, juxtacrine signalling through the α-cell EphA receptors, stimulated by ß-cell ephrin ligands, leads to a tonic inhibition of glucagon secretion. We discuss potential combinations of Ca2+ , cAMP, paracrine and juxtacrine factors in the regulation of glucagon secretion, focusing on recent data in the literature that might unify the field towards a quantitative understanding of α-cell function.