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Laura Muras

Musashi1 Modulates Cell Proliferation Genes in the Medulloblastoma Cell line

Laura Muras

Mentor: Dr. Luiz Penalva

Msi1 is an evolutionarily conserved RNA-binding protein (RBP) that regulates translation by binding to motifs (shapes) of its target mRNA. In mammalian cells, Msi1 has been found to target Numb, a negative regulator of Notch, and p21Cip1, a negative regulator of cyclin-dependent kinases, and recent studies suggest there are additional targets in tumor cells relevant to the cell cycle, apoptosis, proliferation and differentiation. In mammalian cells, Msi1 defines a population of multipotent stem cells in the brain, intestinal crypt cells, breast and hair follicles. Msi1 is also highly expressed in some malignancies, such as medulloblastoma, hepatocellular carcinoma, glioblastoma multiforme, cervical carcinoma, lung cancer and colon cancer. Importantly, reduction of Msi1 by RNAi inhibited the growth of lung cancer cells, as well as colony and neurosphere formation of medulloblastoma cells, suggesting that Msi1 plays an important role in stem cell self-renewal and tumor cell survival. The central hypothesis is that Msi1, through its RNA-binding capacity, regulates the expression of a subset of genes/pathways that are critical for defining &lquot;cancer stem cells& (CSC) and sustaining their viability and growth. This novel means of regulation is a new paradigm in tumor biology that has the potential to reveal novel modes of CSC regulation and new approaches to cancer therapy.

Collaborators: R. Glazer