期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：35
DOI：10.1073/pnas.2205456119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Despite recent therapeutic progress in cancer treatment, the metastatic establishment of cancers at distant organs remains the major cause of mortality in patients with solid tumors. The past decade has brought several advances in the understanding of metabolic phenotypes of tumors that are different from their adjacent nonmalignant tissues. Just recently, attention has been drawn to the fact that metastasizing tumor cells can display dynamic metabolic changes to survive in their changing microenvironment during the metastatic cascade. Here, we perform a comprehensive investigation of the extent of adaptation of metastatic triple negative breast cancer (TNBC) cells to their new microenvironment in the distant tissues. This study could reveal new therapeutic windows for developing more effective treatments of metastatic tumors.
Triple negative breast cancer (TNBC) metastases are assumed to exhibit similar functions in different organs as in the original primary tumor. However, studies of metastasis are often limited to a comparison of metastatic tumors with primary tumors of their origin, and little is known about the adaptation to the local environment of the metastatic sites. We therefore used transcriptomic data and metabolic network analyses to investigate whether metastatic tumors adapt their metabolism to the metastatic site and found that metastatic tumors adopt a metabolic signature with some similarity to primary tumors of their destinations. The extent of adaptation, however, varies across different organs, and metastatic tumors retain metabolic signatures associated with TNBC. Our findings suggest that a combination of anti-metastatic approaches and metabolic inhibitors selected specifically for different metastatic sites, rather than solely targeting TNBC primary tumors, may constitute a more effective treatment approach.
关键词：entriple negative breast cancermetastasisgene expressiongenome-scale metabolic modelssystems biology
