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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
Yujie Hao Yujie Hao 1Mingchen Li Mingchen Li 1Wenxu Liu Wenxu Liu 2Zhenyi Ma Zhenyi Ma 2Zhe Liu Zhe Liu 1*
  • 1 Tianjin Medical University, Tianjin, China
  • 2 Hangzhou Normal University, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    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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