PXD035648

PXD035648 is an original dataset announced via ProteomeXchange.

Title	Exercise forms a metabolic-shield in distant organs blocking cancer progression and metastatic dissemination-Part 2
Description	Exercise prevents cancer incidence and recurrence, yet the underlying mechanism remains mostly unknown. Here we report that exercise induces a metabolic reprogramming of internal organs, increasing their nutrient demand, thus protecting them against metastatic colonization by limiting nutrient availability to the tumor, which we termed exercise induced metabolic-shield. Proteomic and ex-vivo metabolic-capacity analyses of mice internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active subjects' plasma demonstrated increased carbohydrate utilization following exercise. Further, epidemiological data of a 20-year follow-up of a large human cohort of cancer free participants, revealed that exercise prior to cancer initiation has a modest impact on cancer incidence in low metastatic stages, but significantly reduced the likelihood of highly metastatic cancer as compared to inactive participants. We utilized two exercise protocols, wherein the mice were subjected to exercise either both pre- and post- melanoma injection or only pre-injection. We found that exercise prior to cancer injection significantly protects against metastases in distant organs, regardless of the three melanoma metastases models we used. Mechanistically, ex-vivo inhibition of the mTOR pathway, via rapamycin treatment, reversed the protection from the exercise induced metabolic-shield. Under limited glucose conditions, active stroma consumed significantly more glucose, at the expense of the tumor, as reflected in histology analyses of mice melanoma metastases. Our data suggests that cancers’ metabolic plasticity and the exercise-induced metabolic reprogramming of the stroma are clashing, raising the opportunity to block metastases by challenging cancers’ metabolic needs.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:41:04.735.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-01 01:50:06	ID requested
1	2023-03-11 02:47:42	announced
⏵ 2	2023-11-14 08:41:05	announced	2023-11-14: Updated project metadata.

Sheinboim D, Parikh S, Manich P, Markus I, Dahan S, Parikh R, Stubbs E, Cohen G, Zemser-Werner V, Bell RE, Ruiz SA, Percik R, Brenner R, Leibou S, Vaknine H, Arad G, Gerber Y, Keinan-Boker L, Shimony T, Bikovski L, Goldstein N, Constantini K, Labes S, Mordechai S, Doron H, Lonescu A, Ziv T, Nizri E, Choshen G, Eldar-Finkelman H, Tabach Y, Helman A, Ben-Eliyahu S, Erez N, Perlson E, Geiger T, Ben-Zvi D, Khaled M, Gepner Y, Levy C, An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination. Cancer Res, 82(22):4164-4178(2022) [pubmed]

submitter keyword: metabolism, cancer,Exercise

Carmit Levy
contact affiliation	Department of Human Genetics and Biochemistry Sackler School of Medicine Tel Aviv University Tel-Aviv, Israel 69978
contact email	carmitlevy@post.tau.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035648
     1. Label: PRIDE project
     2. Name: Exercise forms a metabolic-shield in distant organs blocking cancer progression and metastatic dissemination-Part 2