Margaret E. Torrence
Massachusetts Institute of Technology
Publications 9
Cell-intrinsic mechanisms of nutrient sensing are intimately linked to adaptive metabolic responses, and these pathways play critical roles in the complex and dynamic nutrient environment of a growing tumor. Nutrient-responsive transcription factors (e.g., HIF, SREBP, ATF4) and signaling pathways (e.g., mTORC1, AMPK) allow tumor cells to tune their metabolic output and strategies to fluctuations in nutrient availability, thus balancing tumor cell proliferation and survival with a combination of ...
3 CitationsSource
#1Ilana Kelsey (Harvard University)H-Index: 1
#2Marie Zbinden (Harvard University)H-Index: 1
Last.Brendan D. Manning (Harvard University)H-Index: 53
view all 5 authors...
The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth that is often aberrantly activated in cancer. However, mTORC1 inhibitors, such as rapamycin, have limited effectiveness as single agent cancer therapies, with feedback mechanisms inherent to the signaling network thought to diminish the anti-tumor effects of mTORC1 inhibition. Here, we identify the protein kinase and proto-oncogene PIM3 as being repressed downstream of mTORC1 signaling. PIM3 expression i...
1 CitationsSource
#1Orianne OlivaresH-Index: 4
#2Jared R. Mayers (MIT: Massachusetts Institute of Technology)H-Index: 14
Last.Sophie VasseurH-Index: 32
view all 20 authors...
Cancer cells adapt their metabolism to survive limited nutrient availability. Here, the authors show that in conditions of limited glucose or glutamine availability, pancreatic ductal adenocarcinoma cells can use collagen-derived proline to foster the TCA cycle and allow…
39 CitationsSource
#1Jared R. Mayers (MIT: Massachusetts Institute of Technology)H-Index: 14
#2Margaret E. Torrence (MIT: Massachusetts Institute of Technology)H-Index: 4
Last.M. Vander HeidenH-Index: 70
view all 17 authors...
Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non–small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-...
148 CitationsSource
#1Brian W. JiH-Index: 2
Last.Mathew G.Vander HeidenH-Index: 71
view all 17 authors...
#1Chen Yuan (Harvard University)H-Index: 12
#2Clary B. Clish (Harvard University)H-Index: 73
Last.Brian M. Wolpin (Harvard University)H-Index: 48
view all 27 authors...
Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown.We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. A...
14 CitationsSource
#1Jared R. Mayers (MIT: Massachusetts Institute of Technology)H-Index: 14
#2Margaret E. Torrence (MIT: Massachusetts Institute of Technology)H-Index: 4
Last.Mathew G.Vander Heiden (MIT: Massachusetts Institute of Technology)H-Index: 71
view all 7 authors...
Introduction: Growth signaling is associated with changes in metabolism in cell culture, but the relatively homogenous nature of culture systems leaves open the question of how specific mutations might behave differently in different tissue contexts. Indeed, previous work has demonstrated that tumor metabolic gene expression most closely resembles the tissue of origin for that tumor1, and that the same oncogenic driver can cause different metabolic phenotypes in different tissues2. We recently f...
#1Jared R. Mayers (MIT: Massachusetts Institute of Technology)H-Index: 14
#2Chen Wu (Harvard University)H-Index: 38
Last.Brian M. Wolpin (Harvard University)H-Index: 48
view all 35 authors...
Elevated plasma levels of branched chain amino acids detected prior to pancreatic cancer diagnosis may result from whole body tissue breakdown occurring during the early stages of this disease.
215 CitationsSource
#1Jared R. MayersH-Index: 14
#2Chen WuH-Index: 38
Last.M. Vander HeidenH-Index: 70
view all 28 authors...