Datasets

Title	Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer
Organism
Number of Samples	6
Release Date	2019/11/04 00:00
Sequencing Types
Protocol Details

Title
Authors	Banh RS, Biancur DE, Yamamoto K, Sohn ASW, Walters B, Kuljanin M, Gikandi A, Wang H, Mancias JD, Schneider RJ, Pacold ME, Kimmelman AC
Journal	Cell
Publication Date	2020 Nov 25
Abstract	Pancreatic ductal adenocarcinoma (PDAC) tumors have a nutrient-poor, desmoplastic, and highly innervated tumor microenvironment. Although neurons can release stimulatory factors to accelerate PDAC tumorigenesis, the metabolic contribution of peripheral axons has not been explored. We found that peripheral axons release serine (Ser) to support the growth of exogenous Ser (exSer)-dependent PDAC cells during Ser/Gly (glycine) deprivation. Ser deprivation resulted in ribosomal stalling on two of the six Ser codons, TCC and TCT, and allowed the selective translation and secretion of nerve growth factor (NGF) by PDAC cells to promote tumor innervation. Consistent with this, exSer-dependent PDAC tumors grew slower and displayed enhanced innervation in mice on a Ser/Gly-free diet. Blockade of compensatory neuronal innervation using LOXO-101, a Trk-NGF inhibitor, further decreased PDAC tumor growth. Our data indicate that axonal-cancer metabolic crosstalk is a critical adaptation to support PDAC growth in nutrient poor environments. Copyright © 2020 Elsevier Inc. All rights reserved.
PMC	PMC8100789
PMID	33142117
DOI

Banh et al. 2020 (PRJNA587516)