scholarly journals Gap Junction Intercellular Communication in the Carcinogenesis Hallmarks: Is This a Phenomenon or Epiphenomenon?

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 896 ◽  
Author(s):  
Zefferino ◽  
Piccoli ◽  
Gioia ◽  
Capitanio ◽  
Conese
Keyword(s):  
Tumor Suppressor ◽  
Small Molecules ◽  
Intercellular Communication ◽  
Cellular Functions ◽  
Therapeutic Implications ◽  
Cancer Hallmarks ◽  
Biological Phenomena ◽  
Gap Junction Intercellular Communication ◽  
Tumor Enhancer

If occupational tumors are excluded, cancer causes are largely unknown. Therefore, it appeared useful to work out a theory explaining the complexity of this disease. More than fifty years ago the first demonstration that cells communicate with each other by exchanging ions or small molecules through the participation of connexins (Cxs) forming Gap Junctions (GJs) occurred. Then the involvement of GJ Intercellular Communication (GJIC) in numerous physiological cellular functions, especially in proliferation control, was proven and accounts for the growing attention elicited in the field of carcinogenesis. The aim of the present paper is to verify and discuss the role of Cxs, GJs, and GJIC in cancer hallmarks, pointing on the different involved mechanisms in the context of the multi-step theory of carcinogenesis. Functional GJIC acts both as a tumor suppressor and as a tumor enhancer in the metastatic stage. On the contrary, lost or non-functional GJs allow the uncontrolled proliferation of stem/progenitor initiated cells. Thus, GJIC plays a key role in many biological phenomena or epiphenomena related to cancer. Depending on this complexity, GJIC can be considered a tumor suppressor in controlling cell proliferation or a cancer ally, with possible preventive or therapeutic implications in both cases.

scholarly journals Microbiota in Pancreatic Diseases: A Review of the Literature

2021 ◽  
Vol 10 (24) ◽  
pp. 5920
Author(s):  
Tommaso Schepis ◽  
Sara S. De Lucia ◽  
Enrico C. Nista ◽  
Vittoria Manilla ◽  
Giulia Pignataro ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Small Molecules ◽  
Bacterial Colonization ◽  
Bacterial Flora ◽  
Critical Element ◽  
High Morbidity ◽  
Pancreatic Diseases ◽  
Therapeutic Implications ◽  
Health And Disease

The gut microbiota is a critical element in the balance between human health and disease. Its impairment, defined as dysbiosis, is associated with gastroenterological and systemic diseases. Pancreatic secretions are involved in the composition and changes of the gut microbiota, and the gut microbiota may colonize the pancreatic parenchyma and be associated with the occurrence of diseases. The gut microbiota and the pancreas influence each other, resulting in a “gut microbiota-pancreas axis”. Moreover, the gut microbiota may be involved in pancreatic diseases, both through direct bacterial colonization and an indirect effect of small molecules and toxins derived from dysbiosis. Pancreatic diseases such as acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer are common gastroenterological diseases associated with high morbidity and mortality. The involvement of the microbiota in pancreatic diseases is increasingly recognized. Therefore, modifying the intestinal bacterial flora could have important therapeutic implications on these pathologies. The aim of this study is to review the literature to evaluate the alterations of the gut microbiota in pancreatic diseases, and the role of the microbiota in the treatment of these diseases.

scholarly journals Recent Synthetic Approaches towards Small Molecule Reactivators of p53

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 635 ◽  
Author(s):  
Jerson L. Silva ◽  
Carolina G. S. Lima ◽  
Luciana P. Rangel ◽  
Giulia D. S. Ferretti ◽  
Fernanda P. Pauli ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Small Molecules ◽  
P53 Protein ◽  
Tp53 Gene ◽  
Therapy Resistance ◽  
Main Function ◽  
Tumor Suppressor Function ◽  
Cellular Functions ◽  
Synthetic Approaches ◽  
Integrity Of Dna

The tumor suppressor protein p53 is often called “the genome guardian” and controls the cell cycle and the integrity of DNA, as well as other important cellular functions. Its main function is to trigger the process of apoptosis in tumor cells, and approximately 50% of all cancers are related to the inactivation of the p53 protein through mutations in the TP53 gene. Due to the association of mutant p53 with cancer therapy resistance, different forms of restoration of p53 have been subject of intense research in recent years. In this sense, this review focus on the main currently adopted approaches for activation and reactivation of p53 tumor suppressor function, focusing on the synthetic approaches that are involved in the development and preparation of such small molecules.

scholarly journals The essential role of tumor suppressor gene ING4 in various human cancers and non-neoplastic disorders

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yang Du ◽  
Yan Cheng ◽  
Guanfang Su
Keyword(s):  
Tumor Suppressor ◽  
Suppressor Gene ◽  
Cancer Hallmarks ◽  
Human Cancers ◽  
Neoplastic Disorders ◽  
And Function ◽  
Transcription Factor P53

AbstractInhibitor of growth 4 (ING4), a member of the ING family discovered in 2003, has been shown to act as a tumor suppressor and is frequently down-regulated in various human cancers. Numerous published in vivo and in vitro studies have shown that ING4 is responsible for important cancer hallmarks such as pathologic cell cycle arrest, apoptosis, autophagy, contact inhibition, and hypoxic adaptation, and also affects tumor angiogenesis, invasion, and metastasis. These characteristics are typically associated with regulation through chromatin acetylation by binding histone H3 trimethylated at lysine 4 (H3K4me3) and through transcriptional activity of transcription factor P53 and NF-κB. In addition, emerging evidence has indicated that abnormalities in ING4 expression and function play key roles in non-neoplastic disorders. Here, we provide an overview of ING4-modulated chromosome remodeling and transcriptional function, as well as the functional consequences of different genetic variants. We also present the current understanding concerning the role of ING4 in the development of neoplastic and non-neoplastic diseases. These studies offer inspiration for pursuing novel therapeutics for various cancers.

Connexin 43 ubiquitination determines the fate of gap junctions: restrict to survive

2015 ◽  
Vol 43 (3) ◽  
pp. 471-475 ◽  
Author(s):  
Teresa M. Ribeiro-Rodrigues ◽  
Steve Catarino ◽  
Maria J. Pinho ◽  
Paulo Pereira ◽  
Henrique Girao
Keyword(s):  
Plasma Membrane ◽  
Gap Junctions ◽  
Gap Junction ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Transmembrane Proteins ◽  
Post Translational Modifications ◽  
Gap Junction Intercellular Communication

Connexins (Cxs) are transmembrane proteins that form channels which allow direct intercellular communication (IC) between neighbouring cells via gap junctions. Mechanisms that modulate the amount of channels at the plasma membrane have emerged as important regulators of IC and their de-regulation has been associated with various diseases. Although Cx-mediated IC can be modulated by different mechanisms, ubiquitination has been described as one of the major post-translational modifications involved in Cx regulation and consequently IC. In this review, we focus on the role of ubiquitin and its effect on gap junction intercellular communication.

scholarly journals Expression and distribution of connexin 32 in rat liver with experimentally induced fibrosis

2009 ◽  
Vol 29 (4) ◽  
pp. 353-357 ◽  
Author(s):  
Alexandro dos S. Rodrigues ◽  
Maria L. Zaidan Dagli ◽  
José L. Avanzo ◽  
Helder P. de Moraes ◽  
Ivone I. Mackowiak ◽  
...  
Keyword(s):  
Small Molecules ◽  
Hepatic Fibrosis ◽  
Intercellular Communication ◽  
Normal Tissue ◽  
Wistar Rats ◽  
Connexin 32 ◽  
Fibrotic Process ◽  
Gap Junction Intercellular Communication ◽  
Female Wistar Rats ◽  
Neoplastic Process

The connexin 32 (Cx32) is a protein that forms the channels that promote the gap junction intercellular communication (GJIC) in the liver, allowing the diffusion of small molecules through cytosol from cell-to-cell. Hepatic fibrosis is characterized by a disruption of normal tissue architeture by cellular lesions, and may alter the GJIC. This work aimed to study the expression and distribution of Cx32 in liver fibrosis induced by the oral administration of dimethylnitrosamine in female Wistar rats. The necropsy of the rats was carried out after five weeks of drug administration. They presented a hepatic fibrosis state. Sections from livers with fibrosis and from control livers were submitted to immunohistochemical, Real Time-PCR and Western-Blot analysis to Cx32. In fibrotic livers the Cxs were diffusely scattered in the cytoplasm, contrasting with the control livers, where the Cx32 formed junction plaques at the cell membrane. Also it was found a decrease in the gene expression of Cx32 without reduction in the protein quantity when compared with controls. These results suggest that there the mechanism of intercellular communication between hepatocytes was reduced by the fibrotic process, which may predispose to the occurrence of a neoplastic process, taken in account that connexins are considered tumor suppressing genes.

IL-1β-induced production of metalloproteinases by synovial cells depends on gap junction conductance

2002 ◽  
Vol 282 (6) ◽  
pp. C1254-C1260 ◽  
Author(s):  
Oleg V. Kolomytkin ◽  
Andrew A. Marino ◽  
David D. Waddell ◽  
J. Michael Mathis ◽  
Robert E. Wolf ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Intercellular Communication ◽  
Biological Function ◽  
Synovial Cells ◽  
Gap Junction Intercellular Communication ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Junction Conductance

Synovial cells can form networks connected by gap junctions. The purpose of this study was to obtain evidence for a necessary role of gap junction intercellular communication in protein secretion by synovial cells. We developed a novel assay to measure the enzymatic activity of metalloproteinases (MMPs) produced by synovial cells in response to interleukin-1β (IL-1β) and employed the assay to explore the biological function of gap junctions. IL-1β produced a dose-dependent increase in MMP activity that was blocked by exposure to the gap junction inhibitors 18α-glycyrrhetinic acid and octanol for as few as 50 min. The inhibitors produced an immediate and marked reduction in intercellular communication, as assessed by transient current analysis using the nystatin perforated-patch method. These observations suggest that communication through gap junctions early in IL-1β signal transduction is critical to the process of cytokine-regulated secretion of MMPs by synovial cells.

scholarly journals Endolysosomal Ca2+ Signalling and Cancer Hallmarks: Two-Pore Channels on the Move, TRPML1 Lags Behind!

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 27 ◽  
Author(s):  
Pawan Faris ◽  
Mudhir Shekha ◽  
Daniela Montagna ◽  
Germano Guerra ◽  
Francesco Moccia
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Neoplastic Transformation ◽  
Cellular Functions ◽  
Membrane Repair ◽  
Multiple Cancer ◽  
Cancer Hallmarks ◽  
Acidic Vesicles ◽  
Transient Receptor

The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca2+ store implicated in the regulation of multiple cellular functions. The EL Ca2+ store releases Ca2+ through a variety of Ca2+-permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca2+ refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca2+ signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca2+ signal through the Ca2+-dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca2+ refilling and release mechanisms and then focus on the oncogenic role of EL Ca2+ signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.

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