Gap junctional intercellular communication is required to maintain embryonic stem cells in a non‐differentiated and proliferative state

Todorova, Mariana G.; Soria, Bernat; Quesada, Iván

doi:10.1002/jcp.21203

Cited by 72 publications

(72 citation statements)

References 41 publications

(128 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, connexin mediated cell-cell adhesion and communication have been shown to be involved in normal stem cell survival and proliferation (Todorova et al, 2008;Cheng et al, 2004;Wong et al, 2006). Also, human and mouse embryonic stem cells as well as human neural progenitors require GJ communication for their survival (Todorova et al, 2008;Cheng et al, 2004;Wong et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Role of connexins in metastatic breast cancer and melanoma brain colonization

Stoletov

Strnádel

Zardouzian

et al. 2013

Journal of Cell Science

157

170

View full text Add to dashboard Cite

SummaryBreast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature. However, it is not known how contact with the vascular niche promotes microtumor formation. Here, we investigate the role of connexins in mediating early events in brain colonization using transparent zebrafish and chicken embryo models of brain metastasis. We provide evidence that breast cancer and melanoma cells utilize connexin gap junction proteins (Cx43, Cx26) to initiate brain metastatic lesion formation in association with the vasculature. RNAi depletion of connexins or pharmacological blocking of connexin-mediated cell-cell communication with carbenoxolone inhibited brain colonization by blocking tumor cell extravasation and blood vessel co-option. Activation of the metastatic gene twist in breast cancer cells increased Cx43 protein expression and gap junction communication, leading to increased extravasation, blood vessel co-option and brain colonization. Conversely, inhibiting twist activity reduced Cx43-mediated gap junction coupling and brain colonization. Database analyses of patient histories revealed increased expression of Cx26 and Cx43 in primary melanoma and breast cancer tumors, respectively, which correlated with increased cancer recurrence and metastasis. Together, our data indicate that Cx43 and Cx26 mediate cancer cell metastasis to the brain and suggest that connexins might be exploited therapeutically to benefit cancer patients with metastatic disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of connexins in metastatic breast cancer and melanoma brain colonization

Stoletov

Strnádel

Zardouzian

et al. 2013

Journal of Cell Science

157

170

View full text Add to dashboard Cite

show abstract

“…using the Cre-lox strategy [18,28]. Given that proliferating cells, some of which may be still undifferentiated progenitors of islet cells, are found at the periphery of fetal and neonatal islets [3,[39][40][41], and that CX43 is usually produced in undifferentiated stem and progenitor cells [42][43][44], further work should investigate whether these cells have any relevance for islet development or repair.…”

Section: Discussionmentioning

confidence: 99%

Beta cell coupling and connexin expression change during the functional maturation of rat pancreatic islets

et al. 2010

View full text Add to dashboard Cite

Aims/hypothesis Cell-cell coupling mediated by gap junctions formed from connexin (CX) contributes to the control of insulin secretion in the endocrine pancreas. We investigated the cellular production and localisation of CX36 and CX43, and gap junction-mediated beta cell coupling in pancreatic islets from rats of different ages, displaying different degrees of maturation of insulin secretion. Methods The presence and distribution of islet connexins were assessed by immunoblotting and immunofluorescence. The expression of connexin genes was evaluated by RT-PCR and quantitative real-time PCR. The ultrastructure of gap junctions and the function of connexin channels were assessed by freeze-fracture electron microscopy and tracer microinjection, respectively. Results Young and adult beta cells, which respond to glucose, expressed significantly higher levels of Cx36 (also known as Gjd2) than fetal and newborn beta cells, which respond poorly to the sugar. Accordingly, adult beta cells also showed a significantly higher membrane density of gap junctions and greater intercellular exchange of ethidium bromide than newborn beta cells. Cx43 (also known as Gja1) was not expressed by beta cells, but was located in various cell types at the periphery of fetal and newborn islets. Conclusions/interpretation These findings show that the pattern of connexins, gap junction membrane density and coupling changes in islets during the functional maturation of beta cells.

show abstract

“…68,69 Recent work also detected expression of a member of the recently discovered pannexin family, Pannexin 2 in postnatal hippocampal neural stem cells with a role in modulating neuronal development. 70 Aquaporin-4, responsible for water and ion homeostasis in the central nervous system, is also expressed in NSCs and plays important roles in the proliferation, survival, migration and neuronal differentiation of adult VZ NSCs via modulation of intracellular Ca 2+ dynamics.…”

Section: Involvement Of Other Types Of Channelsmentioning

confidence: 99%