PXD028632

PXD028632 is an original dataset announced via ProteomeXchange.

Title	Multi-omic Characterization of Pancreatic Cancer-Associated Macrophage Polarization Reveals Deregulated Metabolic Programs Driven by the GMCSF-PI3K Pathway
Description	The pancreatic ductal adenocarcinoma (PDA) microenvironment is composed of a variety of cell types and marked by extensive fibrosis and inflammation. Tumor-associated macrophages (TAM) are abundant, and they are important mediators of disease progression and invasion. TAMs are polarized in situ to a tumor promoting and immunosuppressive phenotype via cytokine signaling and metabolic crosstalk from malignant epithelial cells and other components of the tumor microenvironment (TME). However, the specific distinguishing features and functions of TAMs remain poorly defined. Here, we generated tumor-educated macrophages (TEM) in vitro and performed detailed, multi-omic characterization (i.e. transcriptomics, proteomics, metabolomics). Our results reveal unique genetic and metabolic signatures of TEMs, the veracity of which were queried against our in-house single cell RNA sequencing (scRNA-seq) dataset of human pancreatic tumors. This analysis identified expression of novel, metabolic TEM markers in human pancreatic TAMs, including ARG1, ACLY, and TXNIP. We then utilized our TEM model system to study the role of mutant Kras signaling in cancer cells on TEM polarization. This revealed an important role for GM-CSF and lactate on TEM polarization, molecules released from cancer cells in a mutant Kras-dependent manner. Lastly, we demonstrate that GM-CSF dysregulates TEM gene expression and metabolism through PI3K-AKT pathway signaling. Collectively, our results define new markers and programs to classify pancreatic TAMs, how these are engaged by cancer cells, and the precise signaling pathways mediating polarization.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:56.319.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ho-Joon Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-19 22:01:14	ID requested
1	2022-02-16 14:57:44	announced
2	2022-02-22 06:46:36	announced	2022-02-22: Updated publication reference for PubMed record(s): 35156921.
3	2022-02-22 06:48:01	announced	2022-02-22: Updated publication reference for PubMed record(s): 35156921. 2022-02-22: Updated publication reference for PubMed record(s): 35156921. 2022-02-22: Updated publication reference for DOI(s): 10.7554/eLife.73796.
⏵ 4	2023-11-14 08:53:57	announced	2023-11-14: Updated project metadata.

Boyer S, Lee HJ, Steele N, Zhang L, Sajjakulnukit P, Andren A, Ward MH, Singh R, Basrur V, Zhang Y, Nesvizhskii AI, Pasca di Magliano M, Halbrook CJ, Lyssiotis CA, Multiomic characterization of pancreatic cancer-associated macrophage polarization reveals deregulated metabolic programs driven by the GM-CSF-PI3K pathway. Elife, 11():(2022) [pubmed]

submitter keyword: metabolism, proteomics,macrophage, polarization, LC-MS/MS

Costas A. Lyssiotis
contact affiliation	Department of Molecular & Integrative Physiology, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI 48109, USA
contact email	clyssiot@med.umich.edu
lab head
Ho-Joon Lee
contact affiliation	Yale University
contact email	ho-joon.lee@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028632
     1. Label: PRIDE project
     2. Name: Multi-omic Characterization of Pancreatic Cancer-Associated Macrophage Polarization Reveals Deregulated Metabolic Programs Driven by the GMCSF-PI3K Pathway