A SUMOylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis.

Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the Myc oncogenic program, we used a genome-wide RNA interference screen to search for Myc-synthetic lethal genes and uncovered a role for the SUMO-activating enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc.

Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase.

Among breast cancers, triple-negative breast cancer (TNBC) is the most poorly understood and is refractory to current targeted therapies. Using a genetic screen, we identify the PTPN12 tyrosine phosphatase as a tumor suppressor in TNBC. PTPN12 potently suppresses mammary epithelial cell proliferation and transformation.

The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo.

The discovery of RNAi has revolutionized loss-of-function genetic studies in mammalian systems. However, significant challenges still remain to fully exploit RNAi for mammalian genetics. For instance, genetic screens and in vivo studies could be broadly improved by methods that allow inducible and uniform gene expression control.

Small interference RNA-mediated suppression of overexpressed cyclin E protein restores G1/S regulation in NIH-OVCAR-3 ovarian cancer cells.

The development of ovarian cancer, unlike that of most human tumors, is rarely dependent upon the mutually exclusive loss of RB and p16 cell cycle proteins. RB+/p16+ ovarian cancer cell lines are, however, insensitive to the growth-suppressive effects of ectopically expressed p16 protein, which suggests that they harbor as yet unidentified defects that compromise cell cycle regulation in late G1/S. In the current study, we used Western blotting to analyze cyclin E protein expression in a panel of normal and tumor ovarian tissues and ovarian cancer cell lines (including the p16-insensitive RB+/p16+ ovarian cancer cell line, NIH-OVCAR-3).