0
selected
-
1.
To Detach, Migrate, Adhere, and Metastasize: CD97/ADGRE5 in Cancer.
Aust, G, Zheng, L, Quaas, M
Cells. 2022;(9)
Abstract
Tumorigenesis is a multistep process, during which cells acquire a series of mutations that lead to unrestrained cell growth and proliferation, inhibition of cell differentiation, and evasion of cell death. Growing tumors stimulate angiogenesis, providing them with nutrients and oxygen. Ultimately, tumor cells invade the surrounding tissue and metastasize; a process responsible for about 90% of cancer-related deaths. Adhesion G protein-coupled receptors (aGPCRs) modulate the cellular processes closely related to tumor cell biology, such as adhesion and detachment, migration, polarity, and guidance. Soon after first being described, individual human aGPCRs were found to be involved in tumorigenesis. Twenty-five years ago, CD97/ADGRE5 was discovered to be induced in one of the most severe tumors, dedifferentiated anaplastic thyroid carcinoma. After decades of research, the time has come to review our knowledge of the presence and function of CD97 in cancer. In summary, CD97 is obviously induced or altered in many tumor entities; this has been shown consistently in nearly one hundred published studies. However, its high expression at circulating and tumor-infiltrating immune cells renders the systemic targeting of CD97 in tumors difficult.
-
2.
G Protein-Coupled Estrogen Receptor, GPER1, Offers a Novel Target for the Treatment of Digestive Diseases.
DeLeon, C, Wang, DQ, Arnatt, CK
Frontiers in endocrinology. 2020;:578536
Abstract
There are gender differences between men and women in many physiological functions and diseases, which indicates that female sex hormones may be important. Traditionally, estrogen exerts its biological activities by activating two classical nuclear estrogen receptors, ESR1 and ESR2. However, the roles of estrogen in the regulation of physiological functions and the pathogenesis of diseases become more complicated with the identification of the G protein-coupled estrogen receptor (GPER1). Although many GPER1-specific ligands have been developed, the therapeutic mechanisms of exclusively targeting GPER1 are not yet well understood. Translational applications and clinical trial efforts for the identified GPER1 ligands have been focused primarily on the reproductive, cardiovascular, nervous, endocrine, and immune systems. More recently, research found that GPER1 may play an important role in regulating the digestive system. Cholesterol gallstone disease, a major biliary disease, has a higher prevalence in women than in men worldwide. Emerging evidence implies that GPER1 could play an important role, independent of the classical ESR1, in the pathophysiology of cholesterol gallstones in women. This review discusses the complex signaling pathways of three estrogen receptors, highlights the development of GPER1-specific ligands, and summarizes the latest advances in the role of GPER1 in the pathogenesis of gallstone formation.
-
3.
Expression and Role of the G Protein-Coupled Estrogen Receptor (GPR30/GPER) in the Development and Immune Response in Female Reproductive Cancers.
Hernández-Silva, CD, Villegas-Pineda, JC, Pereira-Suárez, AL
Frontiers in endocrinology. 2020;:544
Abstract
Cancer is a major public health issue and represents the second leading cause of death in women worldwide, as female reproductive-related neoplasms are the main cause of incidence and mortality. Female reproductive cancers have a close relationship to estrogens, the principal female sex steroid hormones. Estrogens exert their actions by the nuclear estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). ERα, and ERβ act as transcription factors mediating genomic effects. Besides, the G protein-coupled estrogen receptor (GPER, formerly known as GPR30) was recently described as a seven-transmembrane receptor that mediates non-genomic estrogenic signaling, including calcium mobilization, cAMP synthesis, cleavage of matrix metalloproteinases, transactivation of epidermal growth factor receptor (EGFR), and the subsequent activation of PI3K and MAPK signaling pathways, which are the reasons why it is related to cellular processes, such as cell-cycle progression, cellular proliferation, differentiation, apoptosis, migration, and invasion. Since its discovery, selective agonists and antagonists have been found and developed. GPER has been implicated in a variety of hormone-responsiveness tumors, such as breast, endometrial, ovarian, cervical, prostate, and testicular cancer as well as lung, hepatic, thyroid, colorectal, and adrenocortical cancers. Nevertheless, GPER actions in cancer are still debatable due to the conflicting information that has been reported to date, since many reports indicate that activation of this receptor can modulate carcinogenesis. In contrast, many others show that its activation inhibits tumor activity. Besides, estrogens play an essential role in the regulation of the immune system, but little information exists about the role of GPER activation on its modulation within cancer context. This review focuses on the role that the stimulation of GPER plays in female reproductive neoplasms, specifically breast, endometrial, ovarian, and cervical cancers, in its tumor activity and immune response regulation.
-
4.
TAS2R38 bitter taste receptor and attainment of exceptional longevity.
Melis, M, Errigo, A, Crnjar, R, Pes, GM, Tomassini Barbarossa, I
Scientific reports. 2019;(1):18047
Abstract
Bitter taste receptors play crucial roles in detecting bitter compounds not only in the oral cavity, but also in extraoral tissues where they are involved in a variety of non‒tasting physiological processes. On the other hand, disorders or modifications in the sensitivity or expression of these extraoral receptors can affect physiological functions. Here we evaluated the role of the bitter receptor TAS2R38 in attainment of longevity, since it has been widely associated with individual differences in taste perception, food preferences, diet, nutrition, immune responses and pathophysiological mechanisms. Differences in genotype distribution and haplotype frequency at the TAS2R38 gene between a cohort of centenarian and near-centenarian subjects and two control cohorts were determined. Results show in the centenarian cohort an increased frequency of subjects carrying the homozygous genotype for the functional variant of TAS2R38 (PAV/PAV) and a decreased frequency of those having homozygous genotype for the non-functional form (AVI/AVI), as compared to those determined in the two control cohorts. In conclusion, our data providing evidence of an association between genetic variants of TAS2R38 gene and human longevity, suggest that TAS2R38 bitter receptor can be involved in the molecular physiological mechanisms implied in the biological process of aging.
-
5.
EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis.
Clottu, AS, Mathias, A, Sailer, AW, Schluep, M, Seebach, JD, Du Pasquier, R, Pot, C
Cell reports. 2017;(1):213-224
Abstract
The interaction between oxysterols and the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2) fine-tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (MS), such as natalizumab. We previously showed that memory CD4+ T lymphocytes migrate specifically in response to 7α,25-dihydroxycholesterol (7α,25-OHC) via EBI2 in the MS murine model experimental autoimmune encephalomyelitis. However, the EBI2 expression profile in human lymphocytes in both healthy and MS donors is unknown. Here, we characterize EBI2 biology in human lymphocytes. We observed that EBI2 is functionally expressed on memory CD4+ T cells and is enhanced under natalizumab treatment. These data suggest a significant role for EBI2 in human CD4+ T cell migration, notably in patients with MS. Better knowledge of EBI2 involvement in autoimmunity may therefore lead to an improved understanding of the physiopathology of MS.
-
6.
Seeing red: flushing out instigators of niacin-associated skin toxicity.
Dunbar, RL, Gelfand, JM
The Journal of clinical investigation. 2010;(8):2651-5
-
-
Free full text
-
Abstract
The use of niacin to improve plasma lipid levels and reduce risk of myocardial infarction is limited by noxious skin effects that result from stimulation of G protein-coupled receptor 109A (GPR109A) in skin immune cells. Niacin causes vasodilation, manifest as rubor (redness) of the head and neck, providing a visible sign associated with other, more bothersome skin complaints. The working theory is that niacin provokes Langerhans cells to produce prostaglandin D2 (PGD2), stimulating vascular DP1 receptors to cause vasodilation. In this issue of the JCI, Hanson and colleagues raise a serious challenge to this paradigm in showing that the major player in vasodilation is the keratinocyte, which produces PGE2, stimulating EP2/4 receptors, shifting the role of the Langerhans/PGD2/DP1 pathway to that of an accomplice. They also show that the antipsoriasis drug monomethyl fumarate, itself a GPR109A agonist, provokes vasodilation through the same cells. These efforts bring us one step closer to solving a key limitation of an important cardioprotective drug and reveal that the skin response to niacin is much more complicated than previously thought.