期刊
CANCER DISCOVERY
卷 12, 期 2, 页码 542-561出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-20-1826
关键词
-
类别
资金
- NIH [CA229803, DK109292, CA236269]
- Cancer Prevention & Research Institute of Texas [RR190029]
- American Gastroentero-logical Association (Caroline Craig and Damian Augustyn Award in Digestive Cancer)
- Albert Einstein Cancer Center [305631]
- Ruth L. Kirschstein T32 [CA200561]
- William C. and Joyce C. O'Neil Charitable Trust
- Ontario Institute for Cancer Research (OICR)
- Canadian Institutes of Health Research [388785]
- Cancer Research Soci-ety [23383]
- Gattuso-Slaight Personalized Cancer Medi-cine Fund from Princess Margaret Cancer Centre
- Abramson Family Cancer Research Institute
- Abramson Cancer Center
- NIH/Penn P30 Center for Molecu-lar Studies in Digestive and Liver Diseases [P30DK050306]
- Memorial Sloan Kettering Single Cell Sequencing Initiative
This study investigated the biological and functional differences driving metastasis in patients with PDAC using a mouse model. The findings revealed an association between the extent of metastasis and gene amplification or transcriptional upregulation of the MYC gene and its downstream targets. Functional experiments demonstrated that MYC promotes metastasis by recruiting tumor-associated macrophages. Further analysis showed that metastatic progression in human PDAC is associated with activation of MYC signaling pathways and MYC amplifications in metastatic patients specifically.
The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological and functional differences that drive the extent of metastasis are poorly understood. We analyzed primary tumors and paired metastases using a multifl uorescent lineage-labeled mouse model of pancreatic ductal adenocarcinoma (PDAC)-a tumor type in which most patients present with metastases. Genomic and transcriptomic analysis revealed an association between metastatic burden and gene amplifi cation or transcriptional upregulation of MYC and its downstream targets. Functional experiments showed that MYC promotes metastasis by recruiting tumor-associated macrophages, leading to greater bloodstream intravasation. Consistent with these fi ndings, metastatic progression in human PDAC was associated with activation of MYC signaling pathways and enrichment for MYC amplifi cations specifi cally in metastatic patients. Collectively, these results implicate MYC activity as a major determinant of metastatic burden in advanced PDAC. SIGNIFICANCE: Here, we investigate metastatic variation seen clinically in patients with PDAC and murine PDAC tumors and identify MYC as a major driver of this heterogeneity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据