Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2022 Volume 24 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2022 Volume 24 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Connexin 43 overexpression induces lung cancer angiogenesis in vitro following phosphorylation at Ser279 in its C‑terminus

  • Authors:
    • Zizi Zhou
    • Wenxiang Chai
    • Yi Liu
    • Yao Liu
    • Huiyu Pan
    • Qiang Wu
    • Xiaoming Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Cardio‑Thoracic Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 293
    |
    Published online on: July 5, 2022
       https://doi.org/10.3892/ol.2022.13413
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Blocking angiogenesis can inhibit tumor growth and metastasis. However, the mechanism underlying regulation of lung cancer angiogenesis remains unclear. The gap junction protein connexin 43 (Cx43) is implicated in angiogenesis. The aim of the present study was to determine the role of Cx43 in angiogenesis in vitro and its signaling pathways. Human pulmonary microvascular endothelial cells were transfected with Cx43‑targeting siRNA or Cx43‑overexpressing recombinant plasmid vector. Reverse transcription‑quantitative polymerase chain reaction and western blotting were performed to determine Cx43, zonula occludens‑1 (ZO‑1), E‑cadherin, β‑catenin, von Willebrand factor (vWF), and plasminogen activator inhibitor‑1 (PAI‑1) mRNA and protein expression levels, respectively. Tyr265, Ser279, Ser368, and Ser373 phosphorylation levels in the C‑terminus of Cx43 and intracellular and membranal Cx43 contents were determined using western blotting. Additionally, immunofluorescence, tube formation, Cell Counting Kit‑8, and Transwell migration assays were performed. The results revealed that compared with that in the control samples, Cx43, ZO‑1, E‑cadherin, β‑catenin, vWF, and PAI‑1 mRNA and protein expression were significantly increased in the Cx43 overexpression group and significantly decreased in the Cx43‑knockdown group. Moreover, the phosphorylation level of Ser279 as well as cell proliferation and migration rates were markedly increased in the Cx43 overexpression group, and tube formation revealed that the potential of angiogenesis was also increased. Conversely, in the Cx43‑knockdown group, the phosphorylation level of Ser279 and cell proliferation and migration rates were reduced, and the potential of angiogenesis was greatly impaired. Under Cx43 overexpression, membranal Cx43 content was significantly increased, whereas under Cx43 knockdown, it was significantly reduced. Therefore, Cx43 overexpression could induce pulmonary angiogenesis in vitro by promoting cell proliferation and migration and activating ZO‑1, E‑cadherin, β‑catenin, vWF, and PAI‑1. This may be achieved by promoting phosphorylation and activation of the intracellular signal site Ser279 at the C‑terminus of Cx43.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Jiang X, Wang J, Deng X, Xiong F, Zhang S, Gong Z, Li X, Cao K, Deng H, He Y, et al: The role of microenvironment in tumor angiogenesis. J Exp Clin Cancer Res. 39:2042020. View Article : Google Scholar : PubMed/NCBI

3 

Saito T, Tanaka R, Wataba K, Kudo R and Yamasaki H: Overexpression of estrogen receptor-alpha gene suppresses gap junctional intercellular communication in endometrial carcinoma cells. Oncogene. 23:1109–1116. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Jiang JX and Gu S: Gap junction- and hemichannel-independent actions of connexins. Biochim Biophys Acta. 1711:208–214. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Goodenough DA and Paul DL: Gap junctions. Cold Spring Harb Perspect Biol. 1:a0025762009. View Article : Google Scholar : PubMed/NCBI

6 

Nielsen MS, Axelsen LN, Sorgen PL, Verma V, Delmar M and Holstein-Rathlou NH: Gap junctions. Compr Physiol. 2:1981–2035. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Saez JC, Berthoud VM, Branes MC, Martinez AD and Beyer EC: Plasma membrane channels formed by connexins: Their regulation and functions. Physiol Rev. 83:1359–1400. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Lampe PD and Lau AF: The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol. 36:1171–1186. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Maeda S and Tsukihara T: Structure of the gap junction channel and its implications for its biological functions. Cell Mol Life Sci. 68:1115–1129. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Roy S, Jiang JX, Li AF and Kim D: Connexin channel and its role in diabetic retinopathy. Prog Retin Eye Res. 61:35–59. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Söhl G and Willecke K: Gap junctions and the connexin protein family. Cardiovasc Res. 62:228–232. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Solan JL and Lampe PD: Connexin phosphorylation as a regulatory event linked to gap junction channel assembly. Biochim Biophys Acta. 1711:154–163. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Meşe G, Richard G and White TW: Gap junctions: Basic structure and function. J Invest Dermatol. 127:2516–2524. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Laws MJ, Taylor RN, Sidell N, DeMayo FJ, Lydon JP, Gutstein DE, Bagchi MK and Bagchi IC: Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival. Development. 135:2659–2668. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Buschmann I, Pries A, Styp-Rekowska B, Hillmeister P, Loufrani L, Henrion D, Shi Y, Duelsner A, Hoefer I, Gatzke N, et al: Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis. Development. 137:2187–2196. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Walker DL, Vacha SJ, Kirby ML and Lo CW: Connexin43 deficiency causes dysregulation of coronary vasculogenesis. Dev Biol. 284:479–498. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Gärtner C, Ziegelhöffer B, Kostelka M, Stepan H, Mohr FW and Dhein S: Knock-down of endothelial connexins impairs angiogenesis. Pharmacol Res. 65:347–357. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Wang HH, Su CH, Wu YJ, Li JY, Tseng YM, Lin YC, Hsieh CL, Tsai CH and Yeh HI: Reduction of connexin43 in human endothelial progenitor cells impairs the angiogenic potential. Angiogenesis. 16:553–560. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Chou Y, Tsai CH, Ueng KC, Tian TY, Chen SC and Yeh HI: Endothelial gap junctions are down-regulated by arsenic trioxide. Eur J Pharmacol. 569:29–36. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Wang HH, Kung CI, Tseng YY, Lin YC, Chen CH, Tsai CH and Yeh HI: Activation of endothelial cells to pathological status by down-regulation of connexin43. Cardiovasc Res. 79:509–518. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Koepple C, Zhou Z, Huber L, Schulte M, Schmidt K, Gloe T, Kneser U, Schmidt VJ and de Wit C: Expression of Connexin43 stimulates endothelial angiogenesis independently of Gap junctional communication in vitro. Int J Mol Sci. 22:74002021. View Article : Google Scholar : PubMed/NCBI

22 

Jansen JA, van Veen TA, de Bakker JM and van Rijen HV: Cardiac connexins and impulse propagation. J Mol Cell Cardiol. 48:76–82. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Schulz R, Görge PM, Görbe A, Ferdinandy P, Lampe PD and Leybaert L: Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection. Pharmacol Ther. 153:90–106. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Omasits U, Ahrens CH, Müller S and Wollscheid B: Protter: Interactive protein feature visualization and integration with experimental proteomic data. Bioinformatics. 30:884–886. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Marsic D, Hughes RC, Byrne-Steele ML and Ng JD: PCR-based gene synthesis to produce recombinant proteins for crystallization. BMC Biotechnol. 8:442008. View Article : Google Scholar : PubMed/NCBI

26 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Distler O, Neidhart M, Gay RE and Gay S: The molecular control of angiogenesis. Int Rev Immunol. 21:33–49. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Polverini PJ: The pathophysiology of angiogenesis. Crit Rev Oral Biol Med. 6:230–247. 1995. View Article : Google Scholar : PubMed/NCBI

29 

Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D and Jain RK: Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 91:1071–1121. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Bir SC, Xiong Y, Kevil CG and Luo J: Emerging role of PKA/eNOS pathway in therapeutic angiogenesis for ischaemic tissue diseases. Cardiovasc Res. 95:7–18. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Carmeliet P and Jain RK: Angiogenesis in cancer and other diseases. Nature. 407:249–257. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Fernandes R, Girão H and Pereira P: High glucose down-regulates intercellular communication in retinal endothelial cells by enhancing degradation of connexin 43 by a proteasome-dependent mechanism. J Biol Chem. 279:27219–27224. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Palatinus JA, Rhett JM and Gourdie RG: The connexin43 carboxyl terminus and cardiac gap junction organization. Biochim Biophys Acta. 1818:1831–1843. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou Z, Chai W, Liu Y, Liu Y, Pan H, Wu Q and Zhang X: Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus. Oncol Lett 24: 293, 2022.
APA
Zhou, Z., Chai, W., Liu, Y., Liu, Y., Pan, H., Wu, Q., & Zhang, X. (2022). Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus. Oncology Letters, 24, 293. https://doi.org/10.3892/ol.2022.13413
MLA
Zhou, Z., Chai, W., Liu, Y., Liu, Y., Pan, H., Wu, Q., Zhang, X."Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus". Oncology Letters 24.3 (2022): 293.
Chicago
Zhou, Z., Chai, W., Liu, Y., Liu, Y., Pan, H., Wu, Q., Zhang, X."Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus". Oncology Letters 24, no. 3 (2022): 293. https://doi.org/10.3892/ol.2022.13413
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Z, Chai W, Liu Y, Liu Y, Pan H, Wu Q and Zhang X: Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus. Oncol Lett 24: 293, 2022.
APA
Zhou, Z., Chai, W., Liu, Y., Liu, Y., Pan, H., Wu, Q., & Zhang, X. (2022). Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus. Oncology Letters, 24, 293. https://doi.org/10.3892/ol.2022.13413
MLA
Zhou, Z., Chai, W., Liu, Y., Liu, Y., Pan, H., Wu, Q., Zhang, X."Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus". Oncology Letters 24.3 (2022): 293.
Chicago
Zhou, Z., Chai, W., Liu, Y., Liu, Y., Pan, H., Wu, Q., Zhang, X."Connexin 43 overexpression induces lung cancer angiogenesis <em>in vitro</em> following phosphorylation at Ser279 in its C‑terminus". Oncology Letters 24, no. 3 (2022): 293. https://doi.org/10.3892/ol.2022.13413
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team