Regulation of SLC6A14 trafficking in breast cancer cells by heat shock protein HSP90β.

Karolina Połosak, Anna Papierniak-Wyglądała, Katarzyna A Nałęcz

Journal: Biochemical and biophysical research communications 2022;614():41-46

PMID: 35569376

Full Text on Elsevier Science View on PubMed

Abstract

SLC6A14 is a plasma membrane transporter specific for neutral and basic amino acids, upregulated in many tumors. This study focused on breast cancer cell lines, showing the fully glycosylated band, known to be at the cell surface, in estrogen receptor positive lines. Inhibition of heat shock protein 90β (HSP90β) decreased the level of this band, what correlated with a decrease of SLC6A14 transport activity. A direct interaction between SLC6A14 and HSP90β was confirmed in proximity ligation assay, pointing to the role of HSP90 in folding control in endoplasmic reticulum and affecting farther transporter trafficking to the cell surface. Either inhibitor of SLC6A14 (α-methyltryptophan) or of HSP90 (radicicol) had the cytotoxic effect, when added alone, while treatment with both compounds had a synergistic effect. This points to SLC6A14 as a druggable target in breast cancer and a combination therapy being more efficient in killing cancer cells.

Address: Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland. Electronic address: [email protected].; Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland. Electronic address: [email protected].; Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland. Electronic address: [email protected].

DOI: 10.1016/j.bbrc.2022.05.011

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MeSH Terms: Amino Acid Transport Systems, Breast Neoplasms, Endoplasmic Reticulum, Female, HSP90 Heat-Shock Proteins, Heat-Shock Proteins, Humans