PXD026738

PXD026738 is an original dataset announced via ProteomeXchange.

Title	LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer
Description	LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Inactivation of Lkb1 accelerates the growth and progression of oncogenic KRAS-driven lung tumors in mouse models. However, the molecular mechanisms by which LKB1 constrains lung tumorigenesis and whether the aggressive cancer state that stems from Lkb1 deficiency can be reverted remains unknown. To identify the processes governed by LKB1 in vivo, we generated an allele which enables Lkb1 inactivation during tumor development and subsequent Lkb1 restoration in established tumors. Restoration of Lkb1 in oncogenic KRAS-driven lung tumors suppressed proliferation and promoted tumor stasis. Lkb1 restoration activated targets of C/EBP transcription factors and drove the transition of neoplastic cells from a progenitor-like state to a less proliferative alveolar type II cell-like state. We show that C/EBP transcription factors govern a subset of genes that are induced by LKB1 and depend upon NKX2-1. We also demonstrate that a defining factor of the alveolar type II lineage, C/EBPα, constrains oncogenic KRAS-driven lung tumor growth. Thus, we uncover a role for a critical tumor suppressor in the regulation of key lineage-specific transcription factors, thereby constraining lung tumor development through the enforcement of differentiation.
HostingRepository	PRIDE
AnnounceDate	2021-12-23
AnnouncementXML	Submission_2021-12-23_11:22:45.942.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026738
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Janos Demeter
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	amidated residue; phosphorylated residue; acetylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-16 04:11:33	ID requested
⏵ 1	2021-12-23 11:22:46	announced

Dataset with its publication pending

submitter keyword: Lung Adenocarcinoma, LKB1, Mouse model, Tumor suppressor

Jackson, Peter, K.
contact affiliation	Baxter Laboratory for Stem Cell Biology Department of Microbiology & Immunology Stanford University School of Medicine 269 Campus Drive CCSR 3205b Stanford, CA 94305-5175, USA
contact email	pjackson@stanford.edu
lab head
Janos Demeter
contact affiliation	Stanford University
contact email	jdemeter@stanford.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026738
     1. Label: PRIDE project
     2. Name: LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer