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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1509183
This article is part of the Research Topic Unlocking Autophagy’s Full Potential: Embracing a Multidimensional Approach for Targeted Cancer Treatment View all 3 articles
Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC
Provisionally accepted- 1 Tianjin Medical University, Tianjin, China
- 2 Hangzhou Normal University, Hangzhou, Zhejiang Province, China
Small cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, driving its aggressive progression and resistance to therapy. Understanding the underlying mechanisms of these features is crucial for improving treatment outcomes. Autophagy, a conserved cellular process, is involved in many cancers, but its role in SCLC remains unclear. Using a genetically engineered mouse model (Rb1 fl/fl ;Trp53 fl/fl ;GFP-LC3-RFP-LC3△G), we tracked autophagic flux in vivo to assess its effects on SCLC biology. Tumor subpopulations with high autophagic flux exhibited increased proliferation, enhanced metastatic potential, and neuroendocrine (NE) characteristics, whereas subpopulations with low autophagic flux exhibited more immune-related signals and non-NE traits. In vitro modulation of autophagic flux further supported these findings: increasing autophagy induced NE features in non-NE cell lines, whereas inhibiting autophagy in NE cell lines promoted non-NE characteristics. This study provides a model for investigating autophagy in vivo and highlights its role in SCLC heterogeneity and plasticity.
Keywords: Autophagic Flux, Small Cell Lung Cancer, SCLC, lineage transition, heterogeneity, plasticity, genetically engineered mouse model
Received: 14 Oct 2024; Accepted: 12 Dec 2024.
Copyright: © 2024 Hao, Li, Liu, Ma and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhe Liu, Tianjin Medical University, Tianjin, China
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