ArticleCancer science2010
Gap junctions sensitize cancer cells to proteasome inhibitor MG132-induced apoptosis.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- MicroRNA-30/Cx43 axis contributes to podocyte injury by regulating ER stress in diabetic nephropathy.Annals of translational medicine · 2020Article
- Protection of normal cells from irradiation bystander effects by silica-flufenamic acid nanoparticles.Journal of materials science. Materials in medicine · 2018Article
- Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition.Molecular medicine reports · 2018Article
- Connexin43 hemichannels contributes to the disassembly of cell junctions through modulation of intracellular oxidative status.Redox biology · 2016Article
- Upregulation of connexin43 contributes to PX-12-induced oxidative cell death.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- A novel TXNIP-based mechanism for Cx43-mediated regulation of oxidative drug injury.Journal of cellular and molecular medicine · 2015Article
- Helicobacter pylori VacA induces apoptosis by accumulation of connexin 43 in autophagic vesicles via a Rac1/ERK-dependent pathway.Cell death discovery · 2015Article
- Dual functions for cytosolic α-mannosidase (Man2C1): its down-regulation causes mitochondria-dependent apoptosis independently of its α-mannosidase activity.The Journal of biological chemistry · 2013Article
- Connexin43 hemichannel-mediated regulation of connexin43.PloS one · 2013Article
- Ubiquitination, intracellular trafficking, and degradation of connexins.Archives of biochemistry and biophysics · 2012Review
- Degradation of connexins through the proteasomal, endolysosomal and phagolysosomal pathways.The Journal of membrane biology · 2012Review
- Activation of Akt, not connexin 43 protein ubiquitination, regulates gap junction stability.The Journal of biological chemistry · 2012Article
- Reciprocal regulation between proinflammatory cytokine-induced inducible NO synthase (iNOS) and connexin43 in bladder smooth muscle cells.The Journal of biological chemistry · 2011Article
- Connexin43 hemichannels contribute to cadmium-induced oxidative stress and cell injury.Antioxidants & redox signaling · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasome inhibition is a promising approach for cancer therapy. However, the mechanisms involved have not been fully elucidated. Gap junctions play important roles in the regulation of tumor cell phenotypes and mediation of the bystander effect in cancer therapy. Because the degradation of gap junction proteins involves the proteasome, we speculated that altered gap junctions might contribute to the antitumor activities of proteasome inhibition. Incubation of Hepa-1c1c7 cells with the proteasome inhibitor MG132 elevated the levels of gap junction protein connexin 43 (Cx43) and promoted gap junctional intercellular communication. This was associated with a marked accumulation of ubiquitylated Cx43 and a significantly decreased rate of Cx43 degradation. The elevated Cx43 contributed to MG132-induced cell apoptosis. This is shown by the observations that: (i) overexpression of Cx43 in the gap junction-deficient LLC-PK1 cells rendered them vulnerable to MG132-elicited cell injury; (ii) fibroblasts derived from Cx43-null mice were more resistant to MG-132 compared with Cx43 wild-type control; and (iii) the gap junction inhibitor flufenamic acid significantly attenuated cell damage caused by MG132 in Hepa-1c1c7 cells. Further studies demonstrated that MG132 activates endoplasmic reticulum stress. Exposure of cells to the endoplasmic reticulum stress inducers thapsigargin and tunicamycin also led to cell apoptosis, which was modulated by Cx43 levels in a way similar to MG132. These results suggested that elevated Cx43 sensitizes cells to MG132-induced cell apoptosis. Regulation of gap junctions could be an important mechanism behind the antitumor activities of proteasome inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.