Dataset Information

PRMT1 inhibition induces differentiation of colon cancer cells

ABSTRACT: Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women, with over 1.8 million new cases in 20181. Differentiation therapy has been recently revisited as a prospective approach in cancer therapy2 by targeting the aberrant growth, differentiation and cell death programs of cancer cells. Standard of care chemotherapy may eradicate cancer cells, but the aggressive cells can survive and resistance gradually develops. In contrast, differentiation therapy aims not to eradicate cancer bulk, but rather directs cancer cells towards inhibited proliferation and restoration of the apoptotic program, while maintaining a limited toxicity. Current data suggests that differentiation therapy can be an effective anti-cancer treatment approach, however discovery of the new differentiation inducing molecules with a higher therapeutic index is essential. We performed HTS screen for compounds mediating differentiation of colon cancer cell using a novel dual multiplex assay3. Here we show that PRMT type 1 inhibitor MS023 is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Our findings has a great importance for following investigation and development of effective differentiation based anti CRC therapy applicable in the clinic.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

SUBMITTER: Meital Kupervaser

LAB HEAD: Barr Haim

PROVIDER: PXD016799 | Pride | 2021-09-09

REPOSITORIES: Pride

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Publications

PRMT1 inhibition induces differentiation of colon cancer cells.

Plotnikov Alexander A Kozer Noga N Cohen Galit G Carvalho Silvia S Duberstein Shirly S Almog Ofir O Solmesky Leonardo Javier LJ Shurrush Khriesto A KA Babaev Ilana I Benjamin Sima S Gilad Shlomit S Kupervaser Meital M Levin Yishai Y Gershovits Michael M Ben-Avraham Danny D Barr Haim Michael HM

Scientific reports 20201118 1

Differentiation therapy has been recently revisited as a prospective approach in cancer therapy by targeting the aberrant growth, and repairing the differentiation and cell death programs of cancer cells. However, differentiation therapy of solid tumors is a challenging issue and progress in this field is limited. We performed High Throughput Screening (HTS) using a novel dual multiplex assay to discover compounds, which induce differentiation of human colon cancer cells. Here we show that the p ...[more]

PMID: 33208761

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Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions. In the study presented here, effusion samples were obtained from 32 patients diagnosed with serous ovarian carcinoma (n=25), primary peritoneal serous carcinoma (n=6) or tubal serous carcinoma (n=1). They were accrued at the Division of Pathology in the Norwegian Radium Hospital from 2000-2006. RNA was used to study the expression profile of 381 multidrug resistant-related genes.

Dataset Information

PRMT1 inhibition induces differentiation of colon cancer cells

Publications

PRMT1 inhibition induces differentiation of colon cancer cells.

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