Effect of depletion of PRSS22 on gene expression of HCT116 colorectal cancer cells

Cancer cells exhibit abnormally altered proteome to satisfy the metabolic demands that arise from heightened proliferation. Trypsin-like serine proteases are a class of proteolytic enzymes whose expression is often dysregulated in cancer. Serine protease 22 (PRSS22) has been associated with the tumorigenesis of several types of tumors. In this study, we identified PRSS22 as a key driver of inflammation to cancer transition (ICT) in colorectal cancer (CRC). PRSS22 expression was positively correlated with the pathological progression of colitis-associated ICT. Genetic disabling of PRSS22 inhibited the growth and migration of and caused redox stress in CRC cells. Mechanistically, knocking down PRSS22 promoted the expression of HMOX1, which fine-tuned the inflammatory response and led to ferroptosis. Loss of PRSS22 also prevented the cleavage of osteopontin and the migratory capacity of CRC cells. We also observed a reduction of M0-to-M2macrophage polarization in a co-culture system of CRC cells and THP-1-derived macrophages. Altogether, this study reveals a tumor-promoting function of PRSS22 as positions it as a key driver in CRC progression. Targeting PRSS22 represents a promising therapeutic strategy against CRC.