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Updated: May 12, 2026
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Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry
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Proteotoxic Stress Triggers Autophagy-Mediated AS160 Degradation and Metabolic Reprogramming in Colorectal Cancer
Somrudee Reabroi1,2, Nareerat Sutjarit3, Arthit Chairoungdua2,4
1Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
ACS Omega
|May 11, 2026
Summary
AS160 protein stability is regulated by autophagy under proteotoxic stress, impacting colon cancer cell lactate handling. Targeting AS160 stability may offer new therapeutic strategies for tumor metabolic adaptation.
Area of Science:
- Molecular Biology
- Cancer Metabolism
- Cellular Stress Response
Background:
- AS160 (TBC1D4) is crucial for glucose transporter trafficking and often overexpressed in cancers.
- Mechanisms controlling AS160 protein stability and its role in colon tumor metabolism are not well understood.
Purpose of the Study:
- To investigate the proteotoxic stress-responsive mechanisms regulating AS160 protein stability.
- To elucidate the contribution of AS160 to colon tumor metabolic adaptation.
Main Methods:
- Utilized proteasome inhibitor MG132 and lysosomal inhibitor chloroquine (CHQ) in colon cancer cell lines (HCT116, HT29).
- Assessed ER stress markers, autophagy markers (p62, LC3-II/LC3-I), and AS160 protein levels.
- Investigated AS160 function via shRNA knockdown, measuring glucose uptake, GLUT1 levels, and lactate secretion/transporter expression (MCT1, MCT4).
Main Results:
- Proteasome inhibition paradoxically reduced AS160 levels, inducing ER stress and autophagy.
- Lysosomal blockade with CHQ caused AS160 accumulation, indicating autophagy-driven turnover.
- AS160 knockdown increased lactate secretion and altered MCT1/MCT4 expression without affecting glucose uptake or GLUT1 levels.
Conclusions:
- AS160 protein stability is regulated by autophagy-associated pathways in response to proteotoxic stress.
- Reduced AS160 expression is linked to altered lactate handling in colon cancer cells.
- Modulating AS160 stability pathways could be a strategy to target tumor metabolic adaptation.
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