Mesenchymal stem cells promote cell invasion and migration and autophagy‐induced epithelial‐mesenchymal transition in A549 lung adenocarcinoma cells

Luo, Dan; Hu, Shiyuan; Tang, Cui; Liu, Guoxiang

doi:10.1002/cbf.3320

Cited by 33 publications

(16 citation statements)

References 39 publications

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“…To summary, these results suggest that the knockdown of miR-133a-3p could promote autophagy, especially in initiation and vesicle nucleation stages under starvation. Besides, considering the miR-133a-3p role on metastasis ability of GC cells and the positive interaction between autophagy and EMT [44, 45] were reported these years, we used western blot to determine the suppressor role of miR-133a-3p on EMT in MKN-45 and BGC-823 GC cells (Fig. 3d).…”

Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis

Zhang

Xuan

et al. 2018

J Exp Clin Cancer Res

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BackgroundAutophagy plays a crucial role in sustaining the homeostasis in various malignant diseases. It has also been reported to promote tumor development in multiple cancers. Glutaminolysis instead of Warburg Effect produce adequate ATP and provide nitrogen and carbon to replenish the TCA cycle which has been discovered to be a new energy source for tumor cells recently. By means of degrading intracellular particles including amino acids, nucleotides, fatty acids, sugars and aged organisms, autophagy can recycle the aforementioned particles into bioenergetics and biosynthesis pathways, finally favoring tumor cells. MicroRNA is a kind of noncoding RNA that regulates the targeting gene expression mostly at post-transcription level. Among these miRNAs, microRNA-133a-3p is reported to be a tumor suppressor in numerous cancers.MethodsWe characterized the down-regulated expression level of microRNA-133a-3p in gastric cancer via TCGA database. Subsequently, we verified the tumor suppressor role of microRNA-133a-3p in gastric cancer cells through a series biological function assay. We used immunofluorescence and transmission electron microscope to observe the negative effect of microRNA-133a-3p on autophagy and used dual-luciferase report assay to identify the candidate gene GABARAPL1 of microRNA-133A-3p.Then we used high performance liquid phase mass spectrometry and seahorse analysis to detect whether miR-133a-3p could block the glutaminolysis metabolism through autophagy. At last, we confirmed the tumor suppressor role of microRNA-133a-3p in vivo on PDX mice model.ResultsWe demonstrated that microRNA-133a-3p overexpression could block the activation of autophagy to ruin the abnormal glutaminolysis and further inhibit the growth and metastasis of gastric cancer cells. We successfully proved gastric cancer cells can replenish glutaminolysis via autophagy and microRNA-133a-3p could block aforementioned pathway by targeting core autophagy participants GABARAPL1 and ATG13.We then verified the negative function of microRNA-133a-3p on autophagy-mediated glutaminolysis both in PDX model and human gastric cancer organoid model.ConclusionsMicroRNA-133a-3p targets GABARAPL1 to block autophagy-mediated glutaminolysis, further repressing gastric cancer growth and metastasis.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0993-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis

Zhang

Xuan

et al. 2018

J Exp Clin Cancer Res

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“…Mast cells are known to interact physically with many cell types and thus to influence the inflammatory phenotype [29][30][31]. Some of the described inflammatory epithelial phenotypes are indeed features of the EMT process [32]. In this study we determined the potential of mast cell-derived EVs to regulate EMT, and we identified the potential signaling events in recipient epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles from mast cells induce mesenchymal transition in airway epithelial cells

et al. 2020

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Background: In the airways, mast cells are present in close vicinity to epithelial cells, and they can interact with each other via multiple factors, including extracellular vesicles (EVs). Mast cell-derived EVs have a large repertoire of cargos, including proteins and RNA, as well as surface DNA. In this study, we hypothesized that these EVs can induce epithelial to mesenchymal transition (EMT) in airway epithelial cells. Methods: In this in-vitro study we systematically determined the effects of mast cell-derived EVs on epithelial A549 cells. We determined the changes that are induced by EVs on A549 cells at both the RNA and protein levels. Moreover, we also analyzed the rapid changes in phosphorylation events in EV-recipient A549 cells using a phosphorylated protein microarray. Some of the phosphorylation-associated events associated with EMT were validated using immunoblotting. Results: Morphological and transcript analysis of epithelial A549 cells indicated that an EMT-like phenotype was induced by the EVs. Transcript analysis indicated the upregulation of genes involved in EMT, including TWIST1, MMP9, TGFB1, and BMP-7. This was accompanied by downregulation of proteins such as E-cadherin and upregulation of Slug-Snail and matrix metalloproteinases. Additionally, our phosphorylated-protein microarray analysis revealed proteins associated with the EMT cascade that were upregulated after EV treatment. We also found that transforming growth factor beta-1, a well-known EMT inducer, is associated with EVs and mediates the EMT cascade induced in the A549 cells. Conclusion: Mast cell-derived EVs mediate the induction of EMT in epithelial cells, and our evidence suggests that this is triggered through the induction of protein phosphorylation cascades.

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“…MSC transplantation may be an effective treatment modality in acute and chronic kidney disease ( 7 ); however, the underlying mechanisms remain unclear. Moreover, MSCs were reported to enhance autophagy in the nervous ( 8 ), digestive ( 9 ), respiratory ( 10 ) and endocrine ( 11 ) systems. However, whether hUC-MSCs increase renal cell autophagy to serve a protective role remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord MSC‑derived hepatocyte growth factor enhances autophagy in AOPP‑treated HK‑2 cells

Zhang

Xie

et al. 2020

Exp Ther Med

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Mesenchymal stem cell (MSC) transplantation may serve as an important treatment modality in chronic kidney disease (CKD); however, the underlying mechanisms remain unclear. Advanced oxidation protein products (AOPP) have been demonstrated to induce renal tubular epithelial cell (RTEC) injury via autophagy inhibition. Therefore, the present study was performed to investigate the role of human umbilical cord-derived MSCs (hUC-MSCs) in RTEC autophagy. AOPP-treated HK-2 cells were co-cultured with hUC-MSCs or treated with recombinant humanized hepatocyte growth factor (HGF). Western blotting was used to detect the levels of autophagy-and PI3K/AKT/mTOR signaling pathway-related proteins, and immunofluorescence staining was used to detect the levels of autophagy-related proteins. The HGF protein levels in HK-2 cells and the hUC-MSC co-culture system were measured. The cells were subsequently treated with tivantinib, an HGF competitive inhibitor, and the levels of autophagy-related proteins were detected. Microtubule-associated protein 1 light chain 3B (LC3B) II/LC3B I (LC3II/LC3I) and beclin 1 protein levels were increased, while p62, PI3K, phosphorylated (p)-AKT and the p-mTOR protein levels were decreased in AOPP-treated HK-2 cells co-cultured with hUC-MSC, compared with the group treated with AOPP only. Furthermore, HGF expression was increased in AOPP-treated HK-2 cells co-cultured with hUC-MSC, compared with the group treated with AOPP alone. When HGF activity was inhibited using tivantinib, these effects on LC3II/LC3I, beclin 1, p62, PI3K, p-AKT, and p-mTOR expression were partially reversed. Furthermore, the effects of tivantinib were reversed by Ly294002. In conclusion, the present study revealed that hUC-MSCs partially reversed AOPP-mediated inhibition of autophagy in HK-2 cells via secretion of HGF, indicating that hUC-MSCs may serve as a potential therapy for preventing the progression of CKD.

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Mesenchymal stem cells promote cell invasion and migration and autophagy‐induced epithelial‐mesenchymal transition in A549 lung adenocarcinoma cells

Cited by 33 publications

References 39 publications

RETRACTED ARTICLE: Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis

RETRACTED ARTICLE: Novel role of miR-133a-3p in repressing gastric cancer growth and metastasis via blocking autophagy-mediated glutaminolysis

Extracellular vesicles from mast cells induce mesenchymal transition in airway epithelial cells

Human umbilical cord MSC‑derived hepatocyte growth factor enhances autophagy in AOPP‑treated HK‑2 cells

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