Gap Junction Protein Connexin43 regulates cellular migration in mouse Glioblastoma cells

Samikshya, S N (2021) Gap Junction Protein Connexin43 regulates cellular migration in mouse Glioblastoma cells. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of S N Samikshya (16MS033)) 16MS033_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (3MB)

Abstract

Glioblastoma is one of the deadliest human brain cancers with high intratumour heterogeneity and low prognosis. Cellular origin of most of the Glioblastoma is known to be the astrocytes; hence it is often termed as grade-IV astrocytoma. Astrocytes are one of the major glial cells that play a vital role in maintaining the central nervous system (CNS) homeostasis. These cells are coupled by gap junctions (GJs) consist of two hexameric hemichannels of the gap junction protein Connexin43 (Cx43). Conventionally Cx43 was known as a tumour suppressor. In high grade cancers including Glioblastoma, a cytoplasmic localization of Cx43 has been reported with an impaired GJ channel formation. Nevertheless, the modern research says beyond tumour suppression, Cx43 acts as a migration enhancer in Glioblastoma. Overall, Cx43 exhibits an opposing role in Glioblastoma progression and metastasis. However, the exact molecular mechanism by which Cx43 expression, localization and functional coupling regulate the cellular migration in Glioblastoma is not yet elaborated. This study reviewed some of these recent findings on the role of Cx43 in Glioblastoma. Two Glioblastoma cell lines with astrocytic origin were selected after a thorough characterization. The state of Cx43 in these two cell lines were Investigated and also compared with healthy primary astrocytes. Interestingly, a differential distribution of Cx43 was found in these two similar origin Glioblastoma cell lines. High resolution Apotome microscope data demonstrated a greater surface expression of Cx43 in the form of GJ plaques in one of the cell lines; whereas the other one showed a cytoplasmic retention. The effects of these alterations on migration properties of Glioblastoma were examined. My studies ultimately showed a positive correlation of the altered surface trafficking of Cx43 with the enhanced rate of migration in high grade astrocytic Glioblastoma.

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