ST14 expression

ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.

The B cancer cells with prostasin expression presented phenotypes consistent with its tumor suppressor role, such as reduced growth and increased apoptosis. Prostasin exosomes could be developed as an agent to initiate the prostasin-matriptase cascade for treating B lymphoma with further studies in animal models.

In this investigation, we first demonstrate clear matriptase activation following Fulvestrant (ICI) and Tykerb (Lapatinib) treatment in HER2-amplified, estrogen receptor (ER)-positive BT474, MDA-MB-361 and ZR-75-30 or single ER-positive MCF7 cells, respectively...We also demonstrate that matriptase activation is not a universal hallmark of stress, with Etoposide treated cells showing a larger degree of matriptase activation than Lapatinib and ICI-treated cells...Novelly, we demonstrate that endogenous and exogenous matriptase activation are ROS-mediated in vitro and inhibited by N-acetylcysteine (NAC). Lastly, we demonstrate matriptase-directed NAC treatment results in apoptosis of several breast cancer cell lines either alone or in combination with clinically used therapeutics. These data demonstrate the contribution of ROS-mediated survival, its independence of kinase-mediated survival, and the plausibility of using matriptase activation to indicate the potential success of antioxidant therapy.

These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.

The ADC was found to be potent and selective against multiple activated matriptase-positive epithelial carcinoma cell lines including triple negative breast cancer (TNBC), as well as alone and in combination with bortezomib in Mantle cell lymphoma (Frontiers in Oncology, 2019,9:258). In-vivo studies showed that the ADC has potent anti-tumor effects alone or in combination with cisplatin or carboplatin against TNBC xenografts and a primary human TNBC (PDX), respectively...The HCC1806 cell line with wt BRCA was sensitive to the ADC and olaparib, but the combination resulted in antagonistic effects. Triple negative breast cancers with a BRAC2 mutation and overexpression of activated matriptase may be a subset of breast cancers that may benefit from the combination of our novel ADC and a PARP inhibitor.