University of Oulu

Khosrowabadi, E., Rivinoja, A., Risteli, M. et al. SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes. Cell. Mol. Life Sci. 78, 6283–6304 (2021). https://doi.org/10.1007/s00018-021-03890-y

SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes

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Author: Khosrowabadi, Elham1; Rivinoja, Antti2; Risteli, Maija3,4;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu (Oulun Yliopisto), Aapistie 7A, PO BOX 5400, 90014, Oulu, Finland
2Present address: Northern Finland Laboratory Centre, Oulu, Finland
3Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
4Medical Research Centre, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021100850452
Language: English
Published: Springer Nature, 2021
Publish Date: 2021-10-08
Description:

Abstract

Proper functioning of each secretory and endocytic compartment relies on its unique pH micro-environment that is known to be dictated by the rates of V-ATPase-mediated H+ pumping and its leakage back to the cytoplasm via an elusive “H+ leak” pathway. Here, we show that this proton leak across Golgi membranes is mediated by the AE2a (SLC4A2a)-mediated bicarbonate-chloride exchange, as it is strictly dependent on bicarbonate import (in exchange for chloride export) and the expression level of the Golgi-localized AE2a anion exchanger. In the acidic Golgi lumen, imported bicarbonate anions and protons then facilitate a common buffering reaction that yields carbon dioxide and water before their egress back to the cytoplasm via diffusion or water channels. The flattened morphology of the Golgi cisternae helps this process, as their high surface-volume ratio is optimal for water and gas exchange. Interestingly, this net acid efflux pathway is often upregulated in cancers and established cancer cell lines, and responsible for their markedly elevated Golgi resting pH and attenuated glycosylation potential. Accordingly, AE2 knockdown in SW-48 colorectal cancer cells was able to restore these two phenomena, and at the same time, reverse their invasive and anchorage-independent growth phenotype. These findings suggest a possibility to return malignant cells to a benign state by restoring Golgi resting pH.

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Series: Cellular and molecular life sciences
ISSN: 1420-682X
ISSN-E: 1420-9071
ISSN-L: 1420-682X
Volume: 78
Issue: 17-18
Pages: 6283 - 6304
DOI: 10.1007/s00018-021-03890-y
OADOI: https://oadoi.org/10.1007/s00018-021-03890-y
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3122 Cancers
Subjects:
Funding: Open access funding provided by University of Oulu including Oulu University Hospital.
Copyright information: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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