scholarly journals A Conceptual Integration of Extra-, Intra- and Gap Junctional- Intercellular Communication in the Evolution of Multi-cellularity and Stem Cells: How Disrupted Cell-Cell Communication during Development can Affect Diseases later in Life

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
James E Trosko
Keyword(s):  
Stem Cells ◽  
Intercellular Communication ◽  
Cell Communication ◽  
Gap Junctional Intercellular Communication ◽  
Conceptual Integration ◽  
Gap Junctional ◽  
Cell Cell

scholarly journals PDGF-AA promotes cell-to-cell communication in osteocytes through PI3K/Akt signaling pathway

2021 ◽  
Author(s):  
Yang Liu ◽  
Mengmeng Duan ◽  
Daimo Guo ◽  
Shiyi Kan ◽  
L i Zhang ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Bone Cells ◽  
Bone Matrix ◽  
Cell Communication ◽  
Akt Signaling ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Mineralized Bone Matrix ◽  
Cell Processes ◽  
Gap Junctional

Abstract Osteocytes are the main sensitive cells in bone remodeling due to their potent functional cell processes from the mineralized bone matrix to the bone surface and the bone marrow. Neighboring osteocytes communicate with each other by these cell processes to achieve molecular exchange through gap junction channels. Platelet-derived growth factor-AA (PDGF-AA) has been reported to enhance bone tissue remodeling by promoting cell proliferation, migration, and autocrine secretion in osteoid cell linage. However, the effect of PDGF-AA on intercellular communication between osteocytes is still unclear. In the present study, we elucidated that PDGF-AA could enhance the formation of dendritic processes of osteocytes and the gap junctional intercellular communication by promoting the expression of connexin43 (Cx43). This modulation process was mainly dependent on the activation of phosphorylation of Akt protein by phosphatidylinositol 3-kinase (PI3K)/Akt (also known as protein kinase B, PKB) signaling. Inhibition of PI3K/Akt signaling decreased the Cx43 expression induced by PDGF-AA. These results establish a bridge between PDGF-AA and cell–cell communication in osteocytes, which could help us understand the molecular exchange between bone cells and fracture healing.

scholarly journals Cancer Prevention and Therapy of Two Types of Gap Junctional Intercellular Communication–Deficient “Cancer Stem Cell”

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 87 ◽  
Author(s):  
James Trosko
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Intercellular Communication ◽  
Adult Stem Cells ◽  
Gap Junctional Intercellular Communication ◽  
Organ Specific ◽  
Connexin Genes ◽  
Gap Junctional

Early observations showed a lack of growth control and terminal differentiation with a lack of gap junctional intercellular communication (GJIC). Subsequent observations showed that epigenetic tumor promoters and activated oncogenes, which block gap junction function, provide insights into the multi-stage, multi-mechanism carcinogenic process. With the isolation of embryonic induced pluri-potent stem cells and organ-specific adult stem cells, gap junctions were linked to early development. While tumors and tumor cell lines are a heterogeneous mixture of “cancer stem cells” and “cancer non-stem cells”, the cancer stem cells seem to be of two types, namely, they express (a) no connexin genes or (b) connexin genes, but do not have functional GJIC. These observations suggest that these “cancer stem cells” originate from normal adult stem cells or from the de-differentiation or re-programming of somatic differentiated cells. This “Concept Paper” provides a hypothesis that “cancer stem cells” either originate from (a) organ-specific adult stem cells before the expression of the connexin genes or (b) organ-specific adult stem cells that just express gap junction genes but that the connexin proteins are rendered dysfunctional by activated oncogenes. Therefore, cancer prevention and therapeutic strategies must account for these two different types of “cancer stem cell”.

scholarly journals Modulation of connexin43 alters expression of osteoblastic differentiation markers

2006 ◽  
Vol 290 (4) ◽  
pp. C1248-C1255 ◽  
Author(s):  
Zhongyong Li ◽  
Zhiyi Zhou ◽  
Marnie M. Saunders ◽  
Henry J. Donahue
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Intercellular Communication ◽  
Cell Communication ◽  
Osteoblastic Differentiation ◽  
Type I ◽  
Mrna Levels ◽  
Gap Junctional Intercellular Communication ◽  
Gap Junctional

Gap junctional channels between cells provide a pathway for exchange of regulatory ions and small molecules. We previously demonstrated that expression of connexins and cell-to-cell communication parallel osteoblastic differentiation and that nonspecific pharmacological inhibitors of gap junctional communication inhibit alkaline phosphatase activity. In this study, we stably transfected connexin (Cx)43 antisense cDNA into the immortalized human fetal osteoblastic cell line hFOB 1.19 (hFOB/Cx43−). hFOB/Cx43− cells express lower levels of Cx43 protein and mRNA and display a 50% decrease in gap junctional intercellular communication relative to control [hFOB/plasmid vector control (pvc)]. This suggests that other connexins, such as Cx45, which is expressed to a similar degree in hFOB/Cx43− cells and hFOB/pvc cells, contribute to cell-to-cell communication in hFOB 1.19 cells. We observed almost total inhibition of alkaline phosphatase activity in hFOB/Cx43− cells despite only a 50% decrease in cell-to-cell communication. This suggests the intriguing possibility that Cx43 expression per se, independent of cell-to-cell communication, influences alkaline phosphatase activity and perhaps bone cell differentiation. Quantitative real-time RT-PCR revealed that mRNA levels for osteocalcin and core binding factor α1 (Cbfa1) increased as a function of time in hFOB/pvc but were inhibited in hFOB/Cx43−. Osteopontin mRNA levels were increased in hFOB/Cx43− relative to hFOB/pvc and decreased as a function of time in both hFOB/Cx43− and hFOB/pvc. Transfection with Cx43 antisense did not affect expression of type I collagen in hFOB 1.19 cells. These results suggest that gap junctional intercellular communication and expression of Cx43 contribute to alkaline phosphatase activity, as well as osteocalcin, osteopontin, and Cbfa1 expression in osteoblastic cells.

scholarly journals Specific N-cadherin–dependent pathways drive human breast cancer dormancy in bone marrow

2021 ◽  
Vol 4 (7) ◽  
pp. e202000969
Author(s):  
Garima Sinha ◽  
Alejandra I Ferrer ◽  
Seda Ayer ◽  
Markos H El-Far ◽  
Sri Harika Pamarthi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Intercellular Communication ◽  
Drug Targets ◽  
Connexin 43 ◽  
Gap Junctional Intercellular Communication ◽  
Bm Niche ◽  
Cancer Dormancy ◽  
Apoptotic Pathways ◽  
Gap Junctional

The challenge for treating breast cancer (BC) is partly due to long-term dormancy driven by cancer stem cells (CSCs) capable of evading immune response and resist chemotherapy. BC cells show preference for the BM, resulting in poor prognosis. CSCs use connexin 43 (Cx43) to form gap junctional intercellular communication with BM niche cells, fibroblasts, and mesenchymal stem cells (MSCs). However, Cx43 is an unlikely target to reverse BC dormancy because of its role as a hematopoietic regulator. We found N-cadherin (CDH2) and its associated pathways as potential drug targets. CDH2, highly expressed in CSCs, interacts intracellularly with Cx43, colocalizes with Cx43 in BC cells within BM biopsies of patients, and is required for Cx43-mediated gap junctional intercellular communication with BM niche cells. Notably, CDH2 and anti-apoptotic pathways maintained BC dormancy. We thereby propose these pathways as potential pharmacological targets to prevent dormancy and chemosensitize resistant CSCs.

Sign in / Sign up

Export Citation Format

Share Document