Genomics

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In vivo RNAi screening identifies regulators of actin dynamics as key determinants of lymphoma progression


ABSTRACT: Mouse models have dramatically improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss of function screening to mouse models of cancer. Using this approach, we have been able to screen nearly 1000 genetic alterations in the context of an individual tumor-bearing mouse. Results from these experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo, and validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of one of these targets, Rac2, potentiated the action of the front-line chemotherapeutic vincristine in vivo, suggesting a critical relationship between tumor cell motility and tumor relapse in hematopoietic malignancies.

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE16090 | GEO | 2009/09/23

SECONDARY ACCESSION(S): PRJNA115455

REPOSITORIES: GEO

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