Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor development

  • Jarosław Czyż Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Katarzyna Piwowarczyk Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Milena Paw Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Marcin Luty Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Tomasz Wróbel Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Jessica Catapano Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Zbigniew Madeja Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Damian Ryszawy Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
Keywords: carcinogenesis, connexin, gap junctions, cellular stress, tumor


Cellular stress responses determine tissue development, homeostasis and pathogenesis. Paracrine signaling, exchange of mechanical stimuli and intercellular transfer of small metabolites via connexin-built gap junctional channels are involved in the cellular stress detection and propagation of stress stimuli in multicellular networks. Cellular stress responses are also regulated through the activity of unpaired connexons (hemichannels) and via the intracellular interference of connexins with the cell cycle and pro-apoptotic machinery. Therefore, connexins are considered as multidirectional transmitters of the "outside-in" and "inside-out" stress signaling that are crucial for tissue homeostasis, regeneration and pathology. In particular, the disturbance of connexin function during the multi-stage process of tumor development leads to abnormal reactions of tumor cells to stress stimuli. In this review, we outline the current knowledge on the multidirectional role of connexins in the detection of stress signals. We also discuss the role of connexin-mediated intercellular transmittance of stress signals in tumour promotion, progression and metastatic cascade.


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