Autophagy–Cholesterol Axis Remodeling Supports Malignant Progression and Chemoresistance in Glioma
Autophagy flux blockade intensifies during progression from astrocytoma to glioblastomaDysregulated autophagy is coupled to altered cholesterol metabolism in malignant gliomasTMZ-resistant glioblastoma cells undergo epithelial-to-mesenchymal transition and mitotic quiescenceResistant cells exhibit constrained bioenergetic capacity and mitochondrial remodelingImpaired autophagy suppresses de novo cholesterol synthesis and lipid recyclingLipidomics reveals accumulation of long-chain cholesteryl esters in TMZ-resistant cellsStatin-based cholesterol inhibition fails to resensitize glioblastoma cells to temozolomide.
Authors
- Abhay Srivastava (ORCID: https://orcid.org/0000-0002-6637-4297)
- Vernon Wayne Dolinsky (ORCID: https://orcid.org/0000-0001-5191-4628)
- Mehdi Eshraghi (ORCID: https://orcid.org/0000-0002-5321-3849)
- Javad Alizadeh (ORCID: https://orcid.org/0000-0001-9082-3083)
- Amir Ravandi
- Sanjiv Dhingra (ORCID: https://orcid.org/0000-0002-2664-7633)
- Grant M. Hatch (ORCID: https://orcid.org/0000-0002-1568-6071)
- Amir Barzegar Behrooz (ORCID: https://orcid.org/0000-0002-8113-5809)
- Vinith Yathindranath (ORCID: https://orcid.org/0000-0002-5053-9704)
- Christopher D. Pascoe (ORCID: https://orcid.org/0000-0002-5229-9927)
- Stevan Pecic (ORCID: https://orcid.org/0000-0002-3706-8768)
- Laura Cole (ORCID: https://orcid.org/0000-0001-8522-6292)
- João Luiz Martins Basso (ORCID: https://orcid.org/0000-0001-8971-121X)
- Tania Dehesh (ORCID: https://orcid.org/0000-0003-0083-0672)
- Courtney Clark
- David M. Miller (ORCID: https://orcid.org/0000-0003-3711-0441)
- Bhavya Bhushan
- Negar Azarpira
- Kianoosh Naghibzadeh
- Simone CDS Rosa
- Shahla Shojaei
- Mateusz Marek Tomczyk
- Roham Saberi
- Rui Vitorino
- Saeid Ghavami
Institutions
- Isfahan University of Medical Sciences (IR)
- California State University, Fullerton (US)
- Universidade do Porto (PT)
- Shiraz University of Medical Sciences (IR)
- Kerman University of Medical Sciences (IR)
- St. Boniface Hospital (CA)
- Children's Hospital Research Institute of Manitoba (CA)
- Rede de Química e Tecnologia (PT)
- University of Manitoba (CA)
- University of Aveiro (PT)
- University of Coimbra (PT)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-01-07
- DOI
- https://doi.org/10.64898/2026.01.06.697885
- Citations
- 1
- Primary Topic
- Cancer, Lipids, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 24.82
Funders
- Research Manitoba
- CancerCare Manitoba Foundation
- Children's Hospital Research Institute of Manitoba
- Canadian Institutes of Health Research
- Fundação para a Ciência e a Tecnologia