engleski

Chronic oxidative stress of extracellular matrix promotes molecular changes associated with breast cancer stem cell phenotype by Hedgehog activation

Oxidative stress plays a role in cancerogenesis, but, on the other hand, it is also a mechanism by which conventional cancer therapy acts. Oxidative stress affects lipids, which results in great variety of reactive aldehydes, among which 4-hydroxynonenal (HNE) is one of the most investigated one. HNE can change cell signaling pathways through with their components. Cancer stem cells are now recognized as a major factor of malignancy by causing metastasis, relapse, cancer treatment failure and therapy resistance. In this study we have evaluated if oxidative stress could change Hedhehog pathway in breast cancer stem cells through interactions of HNE with extracellular matrix represented by collagen I. Our results suggest that oxidative changes in breast cancer stem cell microenvironment in combination with different chronic stressors can cause changes in breast cancer stem cell markers as well as in differentiation markers. Interestingly, chronic stress decreased percentage of putative stem cells, but activated Hedgehog pathway by releasing SuFu inhibition from Gli1. Therefore, chronic stress can lead to decrease in cancer stem cell number, but, in the same time, increase the agressiveness of the remaining cells. These results strongly support the need to study further interactions of oxidative stress, extralellular matrix with singaling pathways within cancer stem cells.

breast cancer stem cells; oxidative stress; extracellular matrix; Hedgehog pathway

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