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Exosomal ITGB6 from dormant lung adenocarcinoma cells activates cancer-associated fibroblasts by KLF10 positive feedback loop and the TGF-ß pathway.
Feng, Xiang; Liu, Xianling; Xiang, Juanjuan; Xu, Jiaqi; Yin, Na; Wang, Lujuan; Liu, Chaoyuan; Liu, Yuyao; Zhao, Tiantian; Zhao, Zengyi; Gao, Yawen.
Afiliación
  • Feng X; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Liu X; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Xiang J; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
  • Xu J; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
  • Yin N; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
  • Wang L; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
  • Liu C; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Liu Y; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Zhao T; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Zhao Z; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Gao Y; Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
Transl Lung Cancer Res ; 12(12): 2520-2537, 2023 Dec 26.
Article en En | MEDLINE | ID: mdl-38205211
ABSTRACT

Background:

Dormant cancer cells are commonly known to play a pivotal role in cancer recurrence and metastasis. However, the mechanism of tumor dormancy and recurrence remains largely unknown. This study aimed to investigate the mechanism by which exosomes derived from dormant lung adenocarcinoma (LUAD) cells activate cancer-associated fibroblasts (CAFs) to reconstruct the extracellular matrix (ECM), providing a novel idea for decoding the mechanism of tumor dormancy.

Methods:

In this study, high-dose cisplatin was used to induce the dormant LUAD cells. Exosomes were extracted from the culture supernatant of normal and dormant cancer cells. The effects of selected exosomal proteins on the fibroblasts were evaluated. RNA-seq for fibroblasts and exosomal proteomics for normal and dormant cancer cells were used to identify and verify the mechanism of activating fibroblasts.

Results:

We demonstrated that exosomes derived from dormant A549 cells could be taken by fibroblasts. Exosomal ITGB6 transferred into fibroblasts induced the activation of CAFs by activating the KLF10 positive feedback loop and transforming growth factor ß (TGF-ß) pathway. High ITGB6 expression was associated with activation of the TGF-ß pathway and ECM remodeling.

Conclusions:

In all, we demonstrated that CAFs were activated by exosomes from dormant lung cancer cells and reconstruct ECM. ITGB6 may be a critical molecule for activating the TGF-ß pathway and remodeling ECM.
Palabras clave

Texto completo: 1 Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Transl Lung Cancer Res Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Transl Lung Cancer Res Año: 2023 Tipo del documento: Article País de afiliación: China