Poster Presentation Australian Epigenetics Alliance Conference 2022

Chromatin remodellor, SMARCB1, plays a more significant role in oncogenesis (#108)

Rasika M Samarasinghe 1 , Sean McGee 1 , Amardeep Dhillon 1
  1. Deakin University, Waurn Ponds, VIC, Australia

SMARCB1, known as the SWItch/Sucrose-Non-Fermentable (SWI/SNF)‐related matrix‐associated regulator of chromatin B 1, is a core sub-unit of the chromatin remodelling complex SWI/SNF, known to be involved in several roles including cell cycle and tumour development(1,2). Loss of SMARCB1 has been found to initiate tumour progression by deregulating cell differentiation and although some evidence has shown the association of SMARCB1 inactivation and tumour growth(3), the molecular mechanisms involved remains to be explored. In our studies, we sought to elucidate some of these mechanisms by investigating the role SMARCB1 played in cellular metabolism, metastasis and invasion. Using SMARCB1 inducible cell lines, the metabolic regulation induced by SMARCB1 was analysed using the Seahorse XF analyser and glycolytic levels were measured. Further, changes in metabolic pathways were analysed using metabolic profile gene arrays. To investigate the metastatic and invasive role of SMARCB1, the Casper IL2Rgc zebrafish xenograft in vivo model was used where SMARCB1 negative cells were injected into specific regions of zebrafish embryos and the pattern of metastasis observed. We found that, cancer cells withoutSMARCB1 showed deregulated metabolism as compared to normal cells and by introducing SMARCB1 these cells significantly shifted its metabolic profile to a more normal and differentiated state. Further, SMARCB1 negative cells had high levels of glycolytic and hypoxic genes expressed, which shifted to a more oxidative state upon introduction of SMARCB1. Interestingly, in the in vivo zebrafish model, SMARCB1 negative cells were observed to be highly metastatic, with cells reaching metastatic sites one day post injection which further confirmed that SMARCB1 plays a critical role in the cancer metastasis and progression. Taken together, our studies have shown that SMARCB1 is not only involved in cell differentiation but also plays a vital role in cancer metabolism and their ability to metastasis and invade to other organs in the body.

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