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Antagonistic functions of connexin 43 during the development of primary or secondary bone tumors

Abstract : Despite research and clinical advances during the past decades, bone cancers remain 11 a leading cause of death worldwide. There is a low survival rate for patients with primary bone 12 tumors such as osteosarcoma and Ewing's sarcoma or secondary bone tumors such as bone 13 metastases from prostate carcinoma. Gap junctions are specialized plasma membrane 14 structures consisting of transmembrane channels that directly link the cytoplasm of adjacent 15 cells, thereby enabling the direct exchange of small signaling molecules between cells. 16 Discoveries of human genetic disorders due to genetic mutations in gap junction proteins 17 (connexins) and experimental data using connexin knockout mice have provided significant 18 evidence that gap junctional intercellular communication (Gj) is crucial for tissue function. 19 Thus, the dysfunction of Gj may be responsible for the development of some diseases. Gj is 20 thus a main mechanism for tumor cells to communicate with other tumor cells and their 21 surrounding microenvironment to survive and proliferate. If it is well accepted that a low level 22 of connexin expression favors cancer cell proliferation and therefore primary tumor 23 development, more evidence is suggesting that a high level of connexin expression stimulates 24 various cellular process such as intravasation, extravasation or migration of metastatic cells. If 25 so, connexin expression would facilitate secondary tumor dissemination. This paper discusses 26 evidence that suggests that connexin 43 plays an antagonistic role in the development of 27 primary bone tumors as a tumor suppressor and secondary bone tumors as a tumor promoter.
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Submitted on : Friday, November 13, 2020 - 2:48:40 PM
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Julie Talbot, Maryne Dupuy, Sarah Morice, Françoise Redini, Franck Verrecchia. Antagonistic functions of connexin 43 during the development of primary or secondary bone tumors. Biomolecules, MDPI, 2020, 10 (9), pp.1240. ⟨10.3390/biom10091240⟩. ⟨inserm-03004043⟩



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