Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC
IntroductionSmall cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, contributing to its aggressive progression and therapy resistance. Autophagy, a conserved cellular process, is implicated in many cancers, but its role in SCLC remains unclear.MethodsUsing a genet...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1509183/full |
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| author | Yujie Hao Mingchen Li Wenxu Liu Zhenyi Ma Zhe Liu Zhe Liu Zhe Liu |
| author_facet | Yujie Hao Mingchen Li Wenxu Liu Zhenyi Ma Zhe Liu Zhe Liu Zhe Liu |
| author_sort | Yujie Hao |
| collection | DOAJ |
| description | IntroductionSmall cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, contributing to its aggressive progression and therapy resistance. Autophagy, a conserved cellular process, is implicated in many cancers, but its role in SCLC remains unclear.MethodsUsing a genetically engineered mouse model (Rb1fl/fl; Trp53fl/fl; GFP-LC3-RFP-LC3△G), we tracked autophagic flux in vivo to investigate its effects on SCLC biology. Additional in vitro experiments were conducted to modulate autophagic flux in NE and non-NE SCLC cell lines.ResultsTumor subpopulations with high autophagic flux displayed increased proliferation, enhanced metastatic potential, and neuroendocrine (NE) characteristics. Conversely, low-autophagic flux subpopulations exhibited immune-related signals and non-NE traits. In vitro, increasing autophagy induced NE features in non-NE cell lines, while autophagy inhibition in NE cell lines promoted non-NE characteristics.DiscussionThis study provides a novel model for investigating autophagy in vivo and underscores its critical role in driving SCLC heterogeneity and plasticity, offering potential therapeutic insights. |
| format | Article |
| id | doaj-art-5046c5a19fe64fbdaf397246cbbb3fe1 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-5046c5a19fe64fbdaf397246cbbb3fe12025-08-20T02:44:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15091831509183Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLCYujie Hao0Mingchen Li1Wenxu Liu2Zhenyi Ma3Zhe Liu4Zhe Liu5Zhe Liu6Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaZhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaZhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaDepartment of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaZhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaCollaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaIntroductionSmall cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, contributing to its aggressive progression and therapy resistance. Autophagy, a conserved cellular process, is implicated in many cancers, but its role in SCLC remains unclear.MethodsUsing a genetically engineered mouse model (Rb1fl/fl; Trp53fl/fl; GFP-LC3-RFP-LC3△G), we tracked autophagic flux in vivo to investigate its effects on SCLC biology. Additional in vitro experiments were conducted to modulate autophagic flux in NE and non-NE SCLC cell lines.ResultsTumor subpopulations with high autophagic flux displayed increased proliferation, enhanced metastatic potential, and neuroendocrine (NE) characteristics. Conversely, low-autophagic flux subpopulations exhibited immune-related signals and non-NE traits. In vitro, increasing autophagy induced NE features in non-NE cell lines, while autophagy inhibition in NE cell lines promoted non-NE characteristics.DiscussionThis study provides a novel model for investigating autophagy in vivo and underscores its critical role in driving SCLC heterogeneity and plasticity, offering potential therapeutic insights.https://www.frontiersin.org/articles/10.3389/fonc.2024.1509183/fullautophagic fluxsmall cell lung cancerSCLClineage transitionheterogeneityplasticity |
| spellingShingle | Yujie Hao Mingchen Li Wenxu Liu Zhenyi Ma Zhe Liu Zhe Liu Zhe Liu Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC Frontiers in Oncology autophagic flux small cell lung cancer SCLC lineage transition heterogeneity plasticity |
| title | Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC |
| title_full | Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC |
| title_fullStr | Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC |
| title_full_unstemmed | Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC |
| title_short | Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC |
| title_sort | autophagic flux modulates tumor heterogeneity and lineage plasticity in sclc |
| topic | autophagic flux small cell lung cancer SCLC lineage transition heterogeneity plasticity |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1509183/full |
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