Abstract
The high level of innervation seen in pancreatic ductal adenocarcinoma tumors supplies serine and serine-deprived conditions promote tumor innervation to support growth in nutrient poor environments.
Original language | English (US) |
---|---|
Pages (from-to) | 1202-1218.e25 |
Journal | Cell |
Volume | 183 |
Issue number | 5 |
DOIs | |
State | Published - Nov 25 2020 |
Keywords
- mRNA translation
- metabolic crosstalk
- neurons
- pancreatic cancer
- serine
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
MD Anderson CCSG core facilities
- Tissue Biospecimen and Pathology Resource
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In: Cell, Vol. 183, No. 5, 25.11.2020, p. 1202-1218.e25.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer
AU - Banh, Robert S.
AU - Biancur, Douglas E.
AU - Yamamoto, Keisuke
AU - Sohn, Albert S.W.
AU - Walters, Beth
AU - Kuljanin, Miljan
AU - Gikandi, Ajami
AU - Wang, Huamin
AU - Mancias, Joseph D.
AU - Schneider, Robert J.
AU - Pacold, Michael E.
AU - Kimmelman, Alec C.
N1 - Funding Information: We acknowledge NYULH Metabolomics Core, Applied Bioinformatics Laboratories, Genome Technology Center, Experimental Pathology Research Laboratory, Microscopy Laboratory, and Ion Channel and Immunology Core for their assistance. These shared resources are partially supported by the NCI Cancer Center Support Grant (P30CA016087) at the Laura and Isaac Perlmutter Cancer Center. We thank Dr. Steven Gygi for use of CORE for mass spectrometry data analysis software and Dr. Tao Pan for providing scripts to analyze the tRNA sequencing data. We thank Raze Therapeutics for PH719. We thank the members of the Kimmelman and Pacold labs for their helpful suggestions and comments. R.S.B. is a Merck Fellow of the Damon Runyon Cancer Research Foundation ( DRG-2348-18 ). D.E.B. is supported by a Ruth L. Kirschstein Institutional National Research Service Award , Levy ( T32 CA009161 ), and the NCI F99/K00 award ( F99 CA245822 ). K.Y. was supported by a Uehara Memorial Foundation Research Fellowship . M.E.P. is supported by a Mary Kay Foundation Cancer Research grant ( 017-32 ), the Shifrin-Myers Breast Cancer Discovery Fund at NYU , a V Foundation V Scholar Grant funded by the Hearst Foundation ( V2017-004 ), and an NCI K22 Career Transition Award ( 1K22CA212059 ). This work was supported by NCI ( R01CA157490 , R01CA188048 , P01CA117969 , and R35CA232124 to A.C.K. and 1RO1CA178509 to R.J.S.), ACS ( RSG-13-298-01-TBG to A.C.K.), NIH ( R01GM095567 to A.C.K. and T32 CA9161-41 to B.W.), the Lustgarten Foundation (to A.C.K.), SU2C (to A.C.K.), Breast Cancer Research Foundation ( BCRF-16-143 to R.J.S.), Burroughs Wellcome Fund Career Award for Medical Scientists (to J.D.M.), Brigham and Women’s Hospital MFCD Award (to J.D.M.), Dana-Farber Cancer Institute-Claudia Adams Barr Program for Innovative Cancer Research Award (to J.D.M.), and the Hale Family Center for Pancreatic Cancer Research (to J.D.M.). Funding Information: We acknowledge NYULH Metabolomics Core, Applied Bioinformatics Laboratories, Genome Technology Center, Experimental Pathology Research Laboratory, Microscopy Laboratory, and Ion Channel and Immunology Core for their assistance. These shared resources are partially supported by the NCI Cancer Center Support Grant (P30CA016087) at the Laura and Isaac Perlmutter Cancer Center. We thank Dr. Steven Gygi for use of CORE for mass spectrometry data analysis software and Dr. Tao Pan for providing scripts to analyze the tRNA sequencing data. We thank Raze Therapeutics for PH719. We thank the members of the Kimmelman and Pacold labs for their helpful suggestions and comments. R.S.B. is a Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-2348-18). D.E.B. is supported by a Ruth L. Kirschstein Institutional National Research Service Award, Levy (T32 CA009161), and the NCI F99/K00 award (F99 CA245822). K.Y. was supported by a Uehara Memorial Foundation Research Fellowship. M.E.P. is supported by a Mary Kay Foundation Cancer Research grant (017-32), the Shifrin-Myers Breast Cancer Discovery Fund at NYU, a V Foundation V Scholar Grant funded by the Hearst Foundation (V2017-004), and an NCI K22 Career Transition Award (1K22CA212059). This work was supported by NCI (R01CA157490, R01CA188048, P01CA117969, and R35CA232124 to A.C.K. and 1RO1CA178509 to R.J.S.), ACS (RSG-13-298-01-TBG to A.C.K.), NIH (R01GM095567 to A.C.K. and T32 CA9161-41 to B.W.), the Lustgarten Foundation (to A.C.K.), SU2C (to A.C.K.), Breast Cancer Research Foundation (BCRF-16-143 to R.J.S.), Burroughs Wellcome Fund Career Award for Medical Scientists (to J.D.M.), Brigham and Women's Hospital MFCD Award (to J.D.M.), Dana-Farber Cancer Institute-Claudia Adams Barr Program for Innovative Cancer Research Award (to J.D.M.), and the Hale Family Center for Pancreatic Cancer Research (to J.D.M.). R.S.B. conceived, designed, and performed most of the experiments; analyzed and interpreted the data; and wrote the manuscript. D.E.B. K.Y. and A.S.W.S. performed mouse surgeries for orthotopic xenografts in the pancreas. D.E.B. collected blood from mice for serum analysis by GC-MS. B.W. and R.J.S. provided expertise on ribosomal profiling and data analysis. H.W. provided and scored IHC samples. M.K. A.G. and J.D.M. performed quantitative proteomics and analyses. M.E.P. provided conceptual advice on serine metabolism. A.C.K. conceived, planned, and guided the research; helped to interpret the data; and wrote the manuscript. All the authors critically analyzed data, edited, and approved the manuscript. M.E.P. has options in Raze Therapeutics and received travel funds from Thermo Fisher Scientific. J.D.M is an inventor on a patent pertaining to the autophagic control of iron metabolism. A.C.K. has financial interests in Vescor Therapeutics, LLC. A.C.K. is an inventor on patents pertaining to KRAS regulated metabolic pathways, redox control pathways in pancreatic cancer, targeting GOT1 as a therapeutic approach, and the autophagic control of iron metabolism. A.C.K is on the Science Advisory Board of Rafael/Cornerstone Pharma. A.C.K. has been a consultant for Deciphera Pharma. The other authors declare no competing interest. Publisher Copyright: © 2020 Elsevier Inc.
PY - 2020/11/25
Y1 - 2020/11/25
N2 - The high level of innervation seen in pancreatic ductal adenocarcinoma tumors supplies serine and serine-deprived conditions promote tumor innervation to support growth in nutrient poor environments.
AB - The high level of innervation seen in pancreatic ductal adenocarcinoma tumors supplies serine and serine-deprived conditions promote tumor innervation to support growth in nutrient poor environments.
KW - mRNA translation
KW - metabolic crosstalk
KW - neurons
KW - pancreatic cancer
KW - serine
UR - http://www.scopus.com/inward/record.url?scp=85096461853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096461853&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.10.016
DO - 10.1016/j.cell.2020.10.016
M3 - Article
C2 - 33142117
AN - SCOPUS:85096461853
SN - 0092-8674
VL - 183
SP - 1202-1218.e25
JO - Cell
JF - Cell
IS - 5
ER -