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Permissive role of Na+/H+ exchanger isoform 1 in migration and invasion of triple-negative basal-like breast cancer cells

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Abstract

In breast cancer, it is the resulting metastasis that is the primary cause of fatality. pH regulatory proteins and the tumor microenvironment play an important role in metastasis of cancer cells and acid-extruding proteins are critical in this process. There are several types of breast cancer and triple-negative breast cancer tends to be more metastatic and invasive and is itself is composed of several types. MDA-MB-468 are a triple-negative breast cancer cell line and are classified as basal-like and basal tumors account for up to 15% of breast cancers. Here we examined the effect of removal of the acid-extruding protein, the Na+/H+ exchanger isoform one, from MDA-MB-468 cells. NHE1 was deleted from these cells using the CRISPR/Cas9 system. Western blotting and measurement of activity confirmed the absence of the protein. In wounding/cell migration experiments, deletion of NHE1 reduced the rate of cell migration in the presence of low- or high-serum concentrations. Anchorage-dependent colony formation was also greatly reduced by deletion of the NHE1 protein. Cell proliferation was not affected by knockout of NHE1. The results demonstrate that NHE1 has an important role in migration and invasion of basal-like triple-negative breast cancer cells.

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Acknowledgements

This research was funded by funding from the Cancer Research Institute of Northern Alberta to LF, Grant Number RES0050041 and by funding from the National Science and Engineering Research Council for Canada RGPIN-2020-03932 to L.F.

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  1. Department of Biochemistry, Faculty of Medicine, University Alberta, Edmonton, AB, T6G 2H7, Canada

    Xiuju Li & Larry Fliegel

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XL produced the data, while L. Fliegel provided the concepts, organized and wrote the manuscript, and provided funding. All authors reviewed and approved the manuscript.

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Correspondence to Larry Fliegel.

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Li, X., Fliegel, L. Permissive role of Na+/H+ exchanger isoform 1 in migration and invasion of triple-negative basal-like breast cancer cells. Mol Cell Biochem 477, 1207–1216 (2022). https://doi.org/10.1007/s11010-022-04370-y

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