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Access Type

WSU Access

Date of Award

January 2022

Degree Type


Degree Name



Cancer Biology

First Advisor

Karin List


TMPRSS13, a type II transmembrane serine protease discovered at the turn of the century, has recently been shown to be significantly overexpressed in both breast cancer (BCa) and colorectal cancer (CRC), and to mediate chemoresistance in cell lines from both cancer types. Furthermore, loss of TMPRSS13 in a genetic model of mouse mammary carcinoma significantly reduced tumor burden and growth rate, and increased overall tumor-free survival. Its location on the cell surface as well as its low expression in normal breast and colon make TMPRSS13 an attractive candidate as an oncogenic biomarker and therapeutic target in cancer. However, little is currently known about the biochemical characteristics and pro-oncogenic mechanisms of TMPRSS13, which are important to understand in order to develop selective and efficacious inhibitors. TMPRSS13 is post-translationally modified by asparagine (N)-linked glycosylation, autoproteolytic cleavage, and intracellular phosphorylation, all of which are interconnected and play a role in the catalytic activity, zymogen activation and cell surface localization of TMPRSS13. Site-directed mutagenesis of N-glycosylated residues and putative cleavage sites in the extracellular domain of TMPRSS13 has revealed that TMPRSS13 must be glycosylated in its catalytic serine protease (SP) domain and cleaved at arginine (R)-223 – localized in the stem region between the low-density lipoprotein receptor class A domain and the scavenger receptor cysteine rich domain – prior to its autoproteolytic zymogen activation at R320. Furthermore, abrogation of SP-domain glycosylation or cleavage at R223 precludes phosphorylation of the intracellular domain of TMPRSS13. The latter observation also relates to the intracellular trafficking of TMPRSS13, as highly phosphorylated TMPRSS13 has been observed on the cell surface. Ongoing mass-spectrometry based experiments to discover binding partners of phosphorylated TMPRSS13 will help to reveal the oncogenic signaling pathways in which cell-surface TMPRSS13 plays a role. The overarching goals of our project are to fully understand how the unique biochemical properties of TMPRSS13 contribute to its enzymatic function and to elucidate the pro-oncogenic mechanisms of TMPRSS13.

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