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Open AccessArticle

SUSD2 Proteolytic Cleavage Requires the GDPH Sequence and Inter-Fragment Disulfide Bonds for Surface Presentation of Galectin-1 on Breast Cancer Cells

Cancer Biology & Immunotherapies Group, Sanford Research, Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57104, USA
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Int. J. Mol. Sci. 2019, 20(15), 3814; https://doi.org/10.3390/ijms20153814
Received: 21 June 2019 / Revised: 24 July 2019 / Accepted: 31 July 2019 / Published: 5 August 2019
(This article belongs to the Special Issue Galectins in Cancer and Translational Research 2.0)
Galectin-1 (Gal-1) is a 14 kDa protein that has been well characterized for promoting cancer metastasis and tumor immune evasion. By localizing to the cancer cell surface, Gal-1 induces T cell apoptosis through binding T cell surface receptors. The transmembrane protein, Sushi Domain Containing 2 (SUSD2), has been previously shown to be required for Gal-1 surface presentation in breast cancer cells. Western immunoblot analysis revealed that SUSD2 is cleaved into two fragments. However, the significance of this cleavage for Gal-1 surface localization has not been investigated. To define the location of cleavage, a mutagenesis analysis of SUSD2 was performed. Our studies demonstrated that SUSD2 is cleaved at its glycine-aspartic acid-proline-histidine (GDPH) amino acid sequence. Generation of a noncleavable SUSD2 mutant (GDPH∆-SUSD2) showed that SUSD2 cleavage was required for SUSD2 and Gal-1 plasma membrane localization. Noncleavable cysteine mutants were also unable to present Gal-1 at the cell surface, further demonstrating that SUSD2 cleavage is required for Gal-1 surface presentation. Treatment with the serine protease inhibitor, Pefabloc SC, inhibited SUSD2 cleavage in a dose dependent manner, suggesting that SUSD2 is cleaved by a serine protease. Therefore, identification and inhibition of this protease may provide a new therapeutic tool for inhibiting SUSD2 and Gal-1′s combined tumorigenic function in breast cancer. View Full-Text
Keywords: breast cancer; SUSD2; galectin-1 breast cancer; SUSD2; galectin-1
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Patrick, M.E.; Egland, K.A. SUSD2 Proteolytic Cleavage Requires the GDPH Sequence and Inter-Fragment Disulfide Bonds for Surface Presentation of Galectin-1 on Breast Cancer Cells. Int. J. Mol. Sci. 2019, 20, 3814.

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