<i>Nm23-H1</i> inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells

Wu, Cunen; Zhuang, Yingping; Zhou, Jin‐Yong; Liu, Shenlin; Zou, Xi; Wu, Jian; Wang, Ruiping; Shu, Ping

doi:10.1515/hsz-2018-0351

Cited by 11 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Curiously, NM23-H1 was (approximately 2.1-fold) downregulated in hypoxia, consistent with our RNAseq data and our observation that NM23-H1 knockdown and overexpression affect the ratio between floating and adherent cells ( Figure 3 and Figure 4 ). This observation is supported by recent studies that show hypoxia reduces NM23-H1 expression in multiple cancer cell lines and that this can facilitate EMT (reduced adhesiveness) and metastasis [ 29 , 30 ]. Indeed, EMT was also identified by pathway analysis as significantly altered ( Supplementary Figure S3 ).…”

Section: Resultssupporting

confidence: 64%

“…Mechanistically, hypoxia has been shown to influence the invasive and migratory behavior of cancer cells via EMT (trans-differentiation of cells in order to acquire plastic and mobile abilities), a process that alters their gene expression prior to migration. Indeed, we see downregulation of the EMT marker E-cadherin in floating cells, which may in part be due to downregulated NM23-H1 expression, a feature we also observed in hypoxia [ 29 , 30 ]. Using the RNAseq data, there is now an opportunity to screen some of the other hypoxia-associated genes that are differentially expressed in floating cells to assay their causative implication in the process of detachment.…”

Section: Discussionmentioning

confidence: 58%

See 1 more Smart Citation

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

Vargas-Accarino

Herrera-Montávez

Cajal

et al. 2021

IJMS

View full text Add to dashboard Cite

There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.

show abstract

Section: Resultssupporting

confidence: 64%

Section: Discussionmentioning

confidence: 58%

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

Vargas-Accarino

Herrera-Montávez

Cajal

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…NME/NM23 nucleoside diphosphate kinase 1 (Nm23) is a key tumor suppressor involved in metastasis regulation and EMT; its deregulation has been associated with dysfunction in metastasis genes. Wu and team identified Wnt/β-catenin cascade as the chief mechanism in nm23-H1-mediated EMT in a hypoxic context in NSCLC [69].…”

Section: The Pi3k/akt Pathwaymentioning

confidence: 99%

Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes

Tirpe

Gulei

Ciortea

et al. 2019

IJMS

254

183

View full text Add to dashboard Cite

Hypoxia represents a frequent player in a number of malignancies, contributing to the development of the neoplastic disease. This review will discuss the means by which hypoxia powers the mechanisms behind cancer progression, with a majority of examples from lung cancer, the leading malignancy in terms of incidence and mortality rates (the frequent reference toward lung cancer is also for simplification purposes and follow up of the global mechanism in the context of a disease). The effects induced by low oxygen levels are orchestrated by hypoxia-inducible factors (HIFs) which regulate the expression of numerous genes involved in cancer progression. Hypoxia induces epithelial-to-mesenchymal transition (EMT) and metastasis through a complex machinery, by mediating various pathways such as TGF-β, PI3k/Akt, Wnt, and Jagged/Notch. Concomitantly, hypoxic environment has a vast implication in angiogenesis by stimulating vessel growth through the HIF-1α/VEGF axis. Low levels of oxygen can also promote the process through several other secondary factors, including ANGPT2, FGF, and HGF. Metabolic adaptations caused by hypoxia include the Warburg effect—a metabolic switch to glycolysis—and GLUT1 overexpression. The switch is achieved by directly increasing the expression of numerous glycolytic enzymes that are isoforms of those found in non-malignant cells.

show abstract

“…Considering more frequent hypoxic features in mesenchymal tumours and higher aggressiveness and metastatic properties allocated to non-epithelial specimens, hypoxia appears as an important mechanism supporting therapy resistance such as chemoresistance in hypoxic tumours. Interestingly, hypoxia-induced features such as EMT appear reversible, offering opportunities for drug development targeting hypoxic related-mechanisms [ 60 , 73 , 74 ].…”

Section: Biological Features Associated With Hypoxia In Nsclcmentioning

confidence: 99%

Hypoxia in Lung Cancer Management: A Translational Approach

Ancel

Perotin

Dewolf

et al. 2021

Cancers

View full text Add to dashboard Cite

Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice. Here, we review clinical and pathological features related to hypoxic lung tumours. Secondly, we expound on the main current techniques to evaluate hypoxic status in NSCLC focusing on positive emission tomography. We present existing alternative experimental approaches such as the examination of circulating markers and highlight the interest in non-invasive markers. Finally, we evaluate the relevance of investigating hypoxia in lung cancer management as a companion biomarker at various lung cancer stages. Hypoxia could support the identification of patients with higher risks of NSCLC. Moreover, the presence of hypoxia in treated tumours could help clinicians predict a worse prognosis for patients with resected NSCLC and may help identify patients who would benefit potentially from adjuvant therapies. Globally, the large quantity of translational data incites experimental and clinical studies to implement the characterisation of hypoxia in clinical NSCLC management.

show abstract

Nm23-H1 inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells

Cited by 11 publications

References 31 publications

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

Spontaneous Cell Detachment and Reattachment in Cancer Cell Lines: An In Vitro Model of Metastasis and Malignancy

Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes

Hypoxia in Lung Cancer Management: A Translational Approach

Contact Info

Product

Resources

About