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Article
GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer
Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). H...
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Article
SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression
Using a Smad4/Pten null transgenic mouse model of prostate cancer, Ding et al. show that the transforming growth factor-β (TGFβ) signalling pathway limits tumour progression and metastasis. By utilizing markers o...
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Article
Open AccessPolygenic in vivovalidation of cancer mutations using transposons
The in vivo validation of cancer mutations and genes identified in cancer genomics is resource-intensive because of the low throughput of animal experiments. We describe a mouse model that allows multiple cancer ...
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Article
Open AccessFunctional annotation of rare gene aberration drivers of pancreatic cancer
As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mu...
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Article
Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer
Targeting tyrosine kinase receptors that share the feedback inhibitor PTPN12 leads to broad spectrum therapeutic suppression of triple-negative breast cancer.
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Article
Open AccessA functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis
Tumor cells disseminate early in tumor development making metastasis-prevention strategies difficult. Identifying proteins that promote the outgrowth of disseminated tumor cells may provide opportunities for n...
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Article
Open AccessTMEM106B drives lung cancer metastasis by inducing TFEB-dependent lysosome synthesis and secretion of cathepsins
Metastatic lung cancer is the leading cause of cancer-associated mortality worldwide, therefore necessitating novel approaches to identify specific genetic drivers for lung cancer progression and metastasis. W...
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Article
Open AccessIn vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer
Genetic aberrations driving pro-oncogenic and pro-metastatic activity remain an elusive target in the quest of precision oncology. To identify such drivers, we use an animal model of KRAS-mutant lung adenocarcino...
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Article
Open AccessRNA editing derived epitopes function as cancer antigens to elicit immune responses
In addition to genomic mutations, RNA editing is another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editing contributes to dif...
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Article
Open AccessNeomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies
Activation of platelet-derived growth factor receptor alpha (PDGFRA) by genomic aberrations contributes to tumor progression in several tumor types. In this study, we characterize 16 novel PDGFRA mutations identi...
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Article
Open AccessThe RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing
Alternative splicing has been shown to causally contribute to the epithelial–mesenchymal transition (EMT) and tumor metastasis. However, the scope of splicing factors that govern alternative splicing in these ...
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Article
PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis
Glioblastoma is a universally lethal form of brain cancer that exhibits an array of pathophysiological phenotypes, many of which are mediated by interactions with the neuronal microenvironment1,2. Recent studies ...
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Article
IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion
Non-small cell lung cancer (NSCLC) is the deadliest form of cancer worldwide, due in part to its proclivity to metastasize. Identifying novel drivers of invasion and metastasis holds therapeutic potential for ...
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Article
Open AccessSimultaneous screening of overexpressed genes in breast cancer for oncogenic drivers and tumor dependencies
There are hundreds of genes typically overexpressed in breast cancer cells and it's often assumed that their overexpression contributes to cancer progression. However, the precise proportion of these overexpre...
