Back to Search
Start Over
CD133 inhibition via autophagic degradation in pemetrexed-resistant lung cancer cells by GMI, a fungal immunomodulatory protein from Ganoderma microsporum
- Source :
- British Journal of Cancer
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
Abstract
- Background Adaptive drug resistance is an unfavourable prognostic factor in cancer therapy. Pemetrexed-resistant lung cancer cells possess high-metastatic ability via ERK–ZEB1 pathway-activated epithelial–mesenchymal transition. GMI is a fungal immunomodulatory protein that suppresses the survival of several cancer cells. Methods Cell viability was analysed by MTT, clonogenic, tumour spheroid, and cancer stem cell sphere assays. Western blot assay was performed to detect the protein expression. Chemical inhibitors and ATG5 shRNA were used to inhibit autophagy. Tumour growth was investigated using xenograft mouse model. Results GMI decreased the viability with short- and long-term effects and induced autophagy but not apoptosis in A549/A400 cells. GMI downregulated the expression levels of CD133, CD44, NANOG and OCT4. GMI induces the protein degradation of CD133 via autophagy. CD133 silencing decreased the survival and proliferation of A549/A400 cells. GMI suppressed the growth and CD133 expression of A549/A400 xenograft tumour. Conclusions This study is the first to reveal the novel function of GMI in eliciting cytotoxic effect and inhibiting CD133 expression in pemetrexed-resistant lung cancer cells via autophagy. Our finding provides evidence that CD133 is a potential target for cancer therapy.
- Subjects :
- Homeobox protein NANOG
Male
Cancer Research
Lung Neoplasms
Cell Survival
ATG5
Drug development
Pemetrexed
Protein degradation
Article
Autophagy-Related Protein 5
Fungal Proteins
03 medical and health sciences
Mice
0302 clinical medicine
Cancer stem cell
Cell Line, Tumor
Macroautophagy
Autophagy
Animals
Humans
Immunologic Factors
Viability assay
AC133 Antigen
Clonogenic assay
030304 developmental biology
Cell Proliferation
0303 health sciences
biology
Chemistry
CD44
Ganoderma
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
Cancer therapeutic resistance
Oncology
A549 Cells
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer cell
embryonic structures
Proteolysis
biology.protein
Cancer research
Lysosomes
Subjects
Details
- Language :
- English
- ISSN :
- 15321827 and 00070920
- Volume :
- 123
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....f976b0d31fcb421519fab2c25870e03a