Unlabelled: Although suppressed cAMP levels have been linked to cancer for nearly five decades, the molecular basis remains uncertain. Here, we identify endosomal pH as a novel regulator of cytosolic cAMP homeostasis and a promoter of transformed phenotypic traits in colorectal cancer. Combining experiments and computational analysis, we show that the Na+/H+ exchanger NHE9 contributes to proton leak and causes luminal alkalinization, which induces resting [Ca2+], and in consequence, represses cAMP levels, creating a feedback loop that echoes nutrient deprivation or hypoxia.
View Article and Find Full Text PDFOral cancer decreases quality of life despite timely medical management. The carcinogens in tobacco products and their role in tumorigenesis are well documented. Langerhans cells (LCs) are a subset of antigen-presenting cells (APCs) that monitor the tumor microenvironment and engulf carcinogens and foreign bodies.
View Article and Find Full Text PDFReceptor Guanylyl Cyclase C (GC-C) was initially characterized as an important regulator of intestinal fluid and ion homeostasis. Recent findings demonstrate that GC-C is also causally linked to intestinal inflammation, dysbiosis, and tumorigenesis. These advances have been fueled in part by identifying mutations or changes in gene expression in GC-C or its ligands, that disrupt the delicate balance of intracellular cGMP levels and are associated with a wide range of clinical phenotypes.
View Article and Find Full Text PDFSinonasal polyps are benign projections of edematous nasal mucosa lined by respiratory epithelium. Langerhans cells (LCs) belonging to the dendritic cell family located in respiratory epithelium are involved in antigen presentation and maintenance of local immunological homeostasis. This study aims to elucidate the morphology and distribution of CD1a positive LCs in normal nasal mucosa and compare the same with polypoid nasal mucosa by immunohistochemistry.
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