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<p>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 cancers. In this study, we identified PRSS22 as a key driver of inflammation-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 <i>HMOX1</i>, which fine-tuned the inflammatory response and led to ferroptosis. Loss of PRSS22 also prevented the cleavage of osteopontin and reduced the migratory capacity of CRC cells. We also observed a reduction of M0-to-M2 macrophage polarization in a co-culture system of CRC cells and THP-1-derived macrophages. Altogether, this study reveals a tumor-promoting function of PRSS22 and positions it as a key driver of CRC progression. Targeting PRSS22 represents a promising therapeutic strategy against CRC.</p>

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PRSS22 inhibits HMOX1-mediated ferroptosis and induces osteopontin cleavage to promote M2 macrophage polarization and colitis-associated carcinogenesis

  • 期刊论文

  • 发表日期：

    2026年3月19日

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  • Zijian Kuang,
  • Qiliang Su,
  • Wenken Liang,
  • Kaikai Shen,
  • Jianling Xie

摘要

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 cancers. In this study, we identified PRSS22 as a key driver of inflammation-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 reduced the migratory capacity of CRC cells. We also observed a reduction of M0-to-M2 macrophage polarization in a co-culture system of CRC cells and THP-1-derived macrophages. Altogether, this study reveals a tumor-promoting function of PRSS22 and positions it as a key driver of CRC progression. Targeting PRSS22 represents a promising therapeutic strategy against CRC.