The role of circadian and redox rhythms in cancer hypoxia

Omer, Sonal; Karunagaran, Devarajan; Suraishkumar, G. K.

doi:10.1016/j.arres.2021.100018

Cited by 4 publications

(1 citation statement)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, it has been shown that the oxygen levels in hypoxic tumor cores are not stable and can fluctuate [ 14 , 15 , 16 , 17 ]. Many potential causes can contribute to this instability in O 2 tension, including pulsation in poorly formed tumor vasculature, mismatch between O 2 consumption and supply, temperate fluctuations, as well as heterogeneity in the metabolic state of cells [ 18 , 19 , 20 , 21 ]. We have also previously shown that highly glycolytic and hypoxic tumor cores may exhibit fluctuations in the transcriptional response of HIF-1, further contributing to the heterogeneity in the hypoxic TME [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells

Novin,

Wali,

Pant

et al. 2024

Cancers

View full text Add to dashboard Cite

Obesity is strongly associated with occurrence, metastasis, and resistance to therapy in breast cancers, which also exhibit high adipose content in the tumor microenvironment. Adipose tissue-derived mesenchymal stromal cells (ASCs) are recruited to breast cancer by many mechanisms, including hypoxia, and contribute to metastatic transition of the cancer. Breast cancers are characterized by regions of hypoxia, which can be temporally unstable owing to a mismatch between oxygen supply and consumption. Using a high-sensitivity nanopatterned stromal invasion assay, we found that ASCs could promote stromal invasion of not only breast cancer cell lines but also MCF10A1, a cell line derived from untransformed breast epithelium. RNA sequencing of MCF10A1 cells conditioned with medium from ASCs revealed upregulation of genes associated with increased cell migration, chemotaxis, and metastasis. Furthermore, we found that fluctuating or oscillating hypoxia could induce senescence in ASCs, which could result in an increased invasive potential in the treated MCF10A1 cells. These findings highlight the complex interplay within the breast cancer microenvironment, hypoxia, and the role of ASCs in transforming even non-cancerous breast epithelium toward an invasive phenotype, providing insights into early metastatic events.

show abstract