The molecular basis underlying the loss of intercellular junctions during cancer pathogenesis and its implications for drug resistance
Intercellular junctions have essential roles in maintaining the integrity of epithelial tissue and in mediating communication between cells. Among the various types of intercellular junctions, the gap junctions are unique in that they consist of arrays of intercellular channels that allow for the direct transfer of ions and small molecules between cells . These channels are formed by a family of transmembrane proteins called connexins, which in humans constitutes 20 members . Gap junctions have numerous essential roles in human physiology, including the regulation of cell proliferation and differentiation and the maintenance of tissue homeostasis . A large body of experimental work indicates that dysregulation of intercellular communication via gap junctions is important in cancer pathogenesis (3)
The objective of this Master's project is two-fold: The first aim is to obtain a better understanding of the molecular mechanisms involved in loss of gap junctions during cancer pathogenesis, with particular emphasis on how dysregulation of post-translational modifications of connexins contributes to such loss. The second aim is to characterize how loss of gap junctions in cancer cells contributes to resistance to chemotherapeutic drugs used in the clinic.
The Master’s student will learn various methods, including DNA/siRNA transfection, confocal microscopy, cell-cell communication assays, co-immunoprecipitation, Western blotting, flow cytometry and gene expression analyses.
The project will be carried out at The Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital (http://www.ous-research.no/molecularoncology/). Our department currently has approximately 40 members, including 10 PhD students and four Master’s students. The Master’ student on this project will work in close collaboration with PhD students and scientists in the department.
Supervisors: Edward Leithe and Ragnhild A. Lothe (internal supervisor)
1. Goodenough DA, Paul DL: Gap junctions. Cold Spring Harb Perspect Biol 2009, 1(1):a002576.
2. Beyer EC, Berthoud VM: Gap junction gene and protein families: Connexins, innexins, and pannexins. Biochim Biophys Acta 2018, 1860(1):5-8.
3. Aasen T, Leithe E, Graham SV, Kameritsch P, Mayan MD, Mesnil M, Pogoda K, Tabernero A: Connexins in cancer: bridging the gap to the clinic. Oncogene 2019, 38(23):4429-4451.