PXD066616-1

PXD066616 is an original dataset announced via ProteomeXchange.

Title	The temporal effect of RMC-7977 treatment on the PANC-1 cell total proteome
Description	KRAS-driven pancreatic ductal adenocarcinoma (PDAC) is dependent on nutrient scavenging pathways to fuel the metabolic demands of proliferation. While acute KRAS loss results in downregulated macropinocytosis, we observed that this downregulation is transient and returns to basal levels in the absence of KRAS. Furthermore, we found that prolonged (7 d) pharmacological inhibition of RAS, KRAS, or MEK resulted in significant upregulation of macropinocytosis. Additionally, we demonstrated that PDAC cells with acquired resistance to RAS inhibitors exhibit a 2- to 10-fold increase in macropinocytosis. Our data suggest We hypothesize that upregulated macropinocytosis may mediate resistance to inhibitors of the RAS ERK-MAPK pathway.  We found that upregulated macropinocytosis in RAS inhibitor-resistant models is accompanied by increased albumin uptake and sensitivity to albumin-bound paclitaxel (nab-paclitaxel). Mechanistically, RAS-inhibitor resistant models exhibit heterogeneous signaling that culminates in increased levels of RAC-GTP, a known driver of macropinocytosis. We conclude that RAS inhibitor-resistant PDAC models upregulate macropinocytosis, which may be exploited for improved delivery of albumin-bound chemotherapeutics.  Within this study, we aimed to evaluate the effects of the pan-RAS inhibitor RMC-7977 on the global proteome of PANC-1 cells. We evaluated the effect at a short-term (24 hour), intermediate (168 hour), and resistant (RASi-R) time points using a global mass spectrometry-based approach.
HostingRepository	PRIDE
AnnounceDate	2026-06-25
AnnouncementXML	Submission_2026-06-25_08:43:59.931.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Scott Lyons
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-26 23:28:06	ID requested
⏵ 1	2026-06-25 08:44:00	announced

Dataset with its publication pending

submitter keyword: RAS inhibitors, resistance, global proteomics, pancreatic cancer

Kirsten L Bryant
contact affiliation	Dept. of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
contact email	bryantkl@email.unc.edu
lab head
Scott Lyons
contact affiliation	UNC Chapel Hill
contact email	scott_lyons@med.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066616
     1. Label: PRIDE project
     2. Name: The temporal effect of RMC-7977 treatment on the PANC-1 cell total proteome