Metabolic rewiring promotes metastatic potential upon glutamine deprivation in STK11 null KRAS-driven lung adenocarcinoma

Presenter's Name(s)

Logan Sands
Shannon Prior

Conference Year

2024

Abstract

Lung adenocarcinoma (LUAD) with concurrent oncogenic KRAS and STK11 loss-of-function mutations define an aggressive cancer subtype. STK11 null cancers are “glutamine addicted” and we have shown glutamine deprivation results in a significant increase in live, detached ∆STK11 cells with the ability to re-adhere and proliferate in full media. Additionally, expression of pro-survival, anti-apoptotic and EMT markers in ∆STK11 cells were increased upon glutamine deprivation. Assessment of O-GlcNAcylation levels revealed that ∆STK11 cells had enhanced HBP flux upon decreasing glutamine availability. We hypothesize that conditions of glutamine stress promote metastatic potential in STK11 null KRAS-driven LUAD due to metabolic rewiring.

Primary Faculty Mentor Name

Paula Deming

Graduate Student Mentors

Shannon Prior

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Biological Science

Primary Research Category

Life Sciences

Abstract only.

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Metabolic rewiring promotes metastatic potential upon glutamine deprivation in STK11 null KRAS-driven lung adenocarcinoma

Lung adenocarcinoma (LUAD) with concurrent oncogenic KRAS and STK11 loss-of-function mutations define an aggressive cancer subtype. STK11 null cancers are “glutamine addicted” and we have shown glutamine deprivation results in a significant increase in live, detached ∆STK11 cells with the ability to re-adhere and proliferate in full media. Additionally, expression of pro-survival, anti-apoptotic and EMT markers in ∆STK11 cells were increased upon glutamine deprivation. Assessment of O-GlcNAcylation levels revealed that ∆STK11 cells had enhanced HBP flux upon decreasing glutamine availability. We hypothesize that conditions of glutamine stress promote metastatic potential in STK11 null KRAS-driven LUAD due to metabolic rewiring.