2. Academic Validation
  3. Low SCRIB expression in fibroblasts promotes invasion of lung cancer cells

Low SCRIB expression in fibroblasts promotes invasion of lung cancer cells

  • Life Sci. 2020 Sep 1;256:117955. doi: 10.1016/j.lfs.2020.117955.
Yuan Wang 1,  Haiyang Liu 2,  Yangyang Bian 1,  Junfeng An 3,  Xixi Duan 1,  Jiajia Wan 1,  Xiaohan Yao 1,  Cancan Du 1,  Chen Ni 1,  Linyu Zhu 1,  Ningjing Lei 1,  Fei Wang 1,  Lijing Zhang 1,  Ming Wang 4,  Zhihai Qin 5
Affiliations

Affiliations

  • 1 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
  • 2 Key Laboratory of Protein and Peptide Pharmaceuticals, CAS-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 3 President of Yun kang Medical Research Institute, Guangzhou, Guangdong 510000, China; School of Yun kang Medical and Health Management, Nan fang College of SUN Yat-Sen University, Guangzhou city, Guangdong 510970, China.
  • 4 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: wangmingheda@163.com.
  • 5 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Key Laboratory of Protein and Peptide Pharmaceuticals, CAS-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Basic Medical Sciences, The Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: zhaihai@ibp.ac.cn.
PMID: 32534038 DOI: 10.1016/j.lfs.2020.117955
Abstract

Aims: Cancer associated fibroblasts (CAFs) play a crucial role in lung tumor development, but the underlying mechanism is still not fully understood.

Main methods: SCRIB expression in the CAFs of human lung Cancer tissues was examined by immunohistochemistry (IHC). A coculture of mouse Lewis lung Cancer cells (LLC) and fibroblasts was used to investigate SCRIB expression in cocultured fibroblasts. Proliferation, scratch wound, and transwell assays were used to examine the proliferation, migration and invasion ability of SCRIB knockdown fibroblasts and their effects on LLC. A 3D-coculture system and co-injection xenograft model were used to examine LLC invasion. RNA Sequencing and transwell experiments were used to explore the molecules that may participate in LLC invasion.

Key findings: Herein, we found that the low expression of SCRIB in CAFs is correlated with advanced tumor stages and poor survival for human lung squamous cell carcinoma. SCRIB expression in fibroblasts is drastically downregulated by LLC cells. SCRIB knockdown fibroblasts not only enhance invasion but also facilitate LLC invasion in a 3D-coculture system and in an in vivo subcutaneous transplantation model. The upregulation of asporin in SCRIB knockdown fibroblasts is involved in LLC invasion in vitro.

Significance: Collectively, the results indicate that fibroblasts with low SCRIB expression promote lung Cancer cell invasion, which suggests that the downregulated expression of SCRIB may represent one of the important characteristics of tumor-promoting CAFs in lung squamous cell Cancer.

Keywords

Asporin; Fibroblasts; Invasion; Lung cancer; SCRIB.

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