Connexins, a family of tetraspan membrane proteins forming intercellular channels localized in gap junctions, play a pivotal role at the different stages of tumor progression presenting both pro- and anti-tumorigenic effects. Considering the potential role of connexins as tumor suppressors through multiple channel-independent mechanisms, their loss of expression may be associated with tumorigenic activity, while it is hypothesized that connexins favor the clonal expansion of tumor cells and promote cell migration, invasion, and proliferation, affecting metastasis and chemoresistance in some cases. Hepatocellular carcinoma (HCC), characterized by unfavorable prognosis and limited responsiveness to current therapeutic strategies, has been linked to gap junction proteins as tumorigenic factors with prognostic value. Notably, several members of connexins have emerged as promising markers for assessing the progression and aggressiveness of HCC, as well as the chemosensitivity and radiosensitivity of hepatocellular tumor cells. Our review sheds light on the multifaceted role of connexins in HCC pathogenesis, offering valuable insights on recent advances in determining their prognostic and therapeutic potential.
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http://dx.doi.org/10.3390/cancers16081533 | DOI Listing |
Int J Mol Sci
January 2025
Programa de Comunicación Celular en Cáncer, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7550000, Chile.
DUX4 is typically a repressed transcription factor, but its aberrant activation in Facioscapulohumeral Muscular Dystrophy (FSHD) leads to cell death by disrupting muscle homeostasis. This disruption affects crucial processes such as myogenesis, sarcolemma integrity, gene regulation, oxidative stress, immune response, and many other biological pathways. Notably, these disrupted processes have been associated, in other pathological contexts, with the presence of connexin (Cx) hemichannels-transmembrane structures that mediate communication between the intracellular and extracellular environments.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Atherosclerosis is a progressive arterial disease arising from imbalanced lipid metabolism and a maladaptive immune response. The lymphatic system ensures tissue fluid homeostasis, absorption of dietary fats and trafficking of immune cells to draining lymph nodes, thereby potentially affecting atherogenesis. Endothelial cell-specific deletion of Pannexin1 (Panx1) in apolipoprotein E-deficient (Apoe-/-) mice increased atherosclerosis, suggesting a protective role for Panx1 channels in arterial endothelial function.
View Article and Find Full Text PDFCancers (Basel)
December 2024
School of Medicine, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Connexin-43 (Cx43) is the most characterized gap junction protein, primarily involved in the Gap Junctional Intercellular Communication (GJIC) between adjacent cells to facilitate molecule exchange and the formation of a signaling network. It is increasingly evident that the importance of Cx43 is not only limited to its GJIC function, but rather includes its role in connecting the intracellular and extracellular environment by forming membrane hemichannels, as well as its intracellular signaling function mediated by its C-terminal tail (Cx43-CT). Notably, Cx43 has been implicated in a variety of cancers, with earlier notions suggesting a tumor-suppressor function, whereas new studies shed light on its pro-tumorigenic role.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative MedicineSchool of Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, 1239 Sanmen Road, Hongkou District, Shanghai, 200434, China.
Background: Perioperative neurocognitive disorder (PND) is a prevalent form of cognitive impairment in elderly patients following anesthesia and surgery. The underlying mechanisms of PND are closely related to perineuronal nets (PNNs). PNNs, which are complexes of extracellular matrix primarily surrounding neurons in the hippocampus, play a critical role in neurocognitive function.
View Article and Find Full Text PDFMol Carcinog
January 2025
Center for Pancreatic Cancer Research, The South China University of Technology School of Medicine, Guangzhou, Guangdong, China.
Pancreatic cancer is a highly lethal malignancy with few effective treatment options. Connexin 31 (Cx31) is a membrane protein capable of forming hexameric channels to facilitate the exchange of metabolites and signaling molecules. Yet, the contribution of Cx31 to the onset and progression of pancreatic cancer remains to be understood.
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