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Title: The plasticity of gastric cancer cell lines
Author: Md Hawari, Muhammad Aizat
ISNI:       0000 0004 9350 0062
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2020
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Cell heterogeneity is a known feature of cancer cell populations. Because of this, cell population behaviour in response to a particular environment may not be replicated in a specific subpopulation. This has prompted a new hypothesis: that cancer cells can undergo phenotypic change to acquire a stem-like cell phenotype. Thus, to determine which sub-population that displays a specific biological function and whether the environment could influence the plasticity of a group of cells within the population is essential. To investigate the potential influence on cell’s plasticity, human gastric cancer cell line SNU-1 was treated with benzo[a]pyrene (BaP), a potent IARC Group I human carcinogen, to induce a phenotypic response. BaP-AhR associated genes (CYPs) (i.e. CYP1a1, CYP1b1, AHR, AHRR, ARNT) and critical genes associated with epithelial to mesenchymal transition (i.e. Snail, TWIST1) and stemness markers (i.e. SOX2, OCT3/4 and NANOG) were examined. We suspected that subpopulations within SNU-1 were involved. Therefore, flow cytometry was used to observe the expression of CD24 and CD166. In unperturbed culture, enriched CD24+ and CD166+ respective cells were found to revert to their original expression phenotype after 72 hours. However, with BaP-treatment, the sorted cells increased surface expression of CD24 and CD166, respectively. Each sorted population (CD24+, CD166+ and CD24-CD166-) showed different regulation of genes associated with stemness and BaP-induced phenotypic change. CTNNB1, a target gene of Wnt/β-catenin signalling pathway, MYC, and EMT-inducer genes were upregulated in the unsorted SNU-1 population and sorted CD24+ (BaP 10-7M to 10-5M) while remained unchanged in CD166+ and CD24-CD166- populations. Moreover, the induced expression of AhR-related and stemness genes in the sorted CD24+ population, potentially indicates that this subpopulation probably contributes to the plasticity of SNU-1. BaP- treatment also mediates changes in stemness expression and enhanced its migrative and invasive capabilities. Thus, the co-existence and interaction of subpopulations within SNU-1 could play a role in cell plasticity and in sustaining key signalling pathway responses and stemness when exposed to BaP. Our data suggest that cell heterogeneity and plasticity of subpopulations within gastric cancer cells could contribute to BaP-induced gastric carcinogenicity.
Supervisor: Gooderham, Nigel Sponsor: Universiti Putra Malaysia ; Yayasan Daya Diri
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral