The serine protease PRSS8 has shown important physiological and pathological functions, but its roles in cancer initiation and progression are unclear. We developed and dynamically characterized a conditional knockout Prss8^fl/fl, p-Villin-Cre⁺ mouse model. We found that genetic deficiency of the Prss8 gene caused spontaneous colitis and an inflamed rectum at an early age and caused intestinal tumors at a late age, which were linked to increased intestinal cell proliferation and migration but decreased cell differentiation. Increased PRSS8 expression inhibited cancer cell growth and metastasis in nude mice and inhibited cancer cell migration, invasion, colony formation and tumor sphere formation in vitro, but decreased PRSS8 expression facilitated malignancies in vivo and in vitro. Gene profiling on manipulated cancer cells and intestinal epithelial cells of Prss8 mouse models, gene set enrichment analysis and mechanistic studies revealed that PRSS8 targeted the Wnt/β-catenin, epithelial-mesenchymal transition, and stem cell signaling pathways, which were further supported by the results from the TCGA data mining and validated by immunohistochemical staining on colorectal cancer tissue microarrays. In conclusion, PRSS8 is a novel tumor suppressor that plays critical roles in the suppression of colorectal carcinogenesis and metastasis.

中文翻译：

---

PRSS8抑制大肠癌的发生和转移。

丝氨酸蛋白酶PRSS8已显示出重要的生理和病理功能，但在癌症的发生和发展中的作用尚不清楚。我们开发并动态表征了条件敲除Prss8 ^{fl / fl}，p-Villin-Cre ⁺鼠标模型。我们发现，Prss8基因的遗传缺陷在早年引起自发性结肠炎和直肠发炎，在晚年引起肠道肿瘤，这与肠道细胞增殖和迁移增加但细胞分化减少有关。PRSS8表达的增加抑制了裸鼠体内癌细胞的生长和转移，并在体外抑制了癌细胞的迁移，侵袭，集落形成和肿瘤球的形成，但PRSS8表达的降低促进了体内和体外的恶性肿瘤。Prss8小鼠模型的可操纵癌细胞和肠上皮细胞的基因概况分析，基因集富集分析和机制研究表明，PRSS8靶向Wnt /β-catenin，上皮-间质转化和干细胞信号传导途径，TCGA数据挖掘的结果进一步支持了这一点，并通过在结肠直肠癌组织微阵列上进行的免疫组织化学染色进行了验证。总之，PRSS8是一种新型的肿瘤抑制因子，在抑制结直肠癌的发生和转移中起着至关重要的作用。