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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
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3814;
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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MDPI and ACS Style

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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