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 cleav... More
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.
