Poster Presentation 29th Lorne Cancer Conference 2017

SMCHD1 regulates epithelial-to-mesenchymal transition in 5-FU drug resistant colorectal cancer cells (#102)

Nidhi Abraham 1 , Lahiru Gangoda 1 , Suresh Mathivanan 1
  1. La Trobe Institute for Molecular Science, Bundoora, VIC, Australia

In patients with metastatic cancer, chemotherapy is the choice of treatment. Additionally, in patients with metastatic colorectal cancer (CRC), 5- Fluorouracil (5-FU) based combination therapy is the current approach which has been shown to improve survival rates in nearly 50 % of patients. However, one of the major hurdles is the development of chemoresistance which leads to treatment failure. Hence, it is critical to understand the molecular mechanisms involved in acquired chemotherapeutic drug resistance in order to develop novel strategies to combat resistance. Preliminary quantitative proteomic analysis identified the epigenetic modifier protein SMCHD1 to be upregulated in 5-FU resistant SW620 CRC cells in comparison to its parental cells. In order to better understand the role of SMCHD1 in chemoresistance to 5-FU, a panel of CRC cells were made resistant to 5-FU by long term exposure to increasing concentrations of the drug and follow up Western blotting and proteomic analysis revealed an upregulation in SMCHD1 in the resistant cells. Furthermore, knockout of SMCHD1 using gene editing techniques showed epithelial-to-mesenchymal (EMT) markers to be regulated suggesting SMCHD1 to have a role in the regulation of EMT. In addition, co-immunoprecipitation assay followed by proteomic analysis was conducted to identify interacting partners of SMCHD1.