{
  "abstract": "High-temperature requirement protease A3 (HtrA3) has been implicated in the progression of various carcinomas through tissue-specific mechanisms; however, its precise role in colorectal cancer (CRC) remains unclear. We initially identified the upregulation of HtrA3 in CRC tissues through Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) proteomics, which was consistent with the analysis of the CPTAC dataset. Our research further confirmed that HtrA3 is significantly upregulated in CRC tissues and associated with reduced overall survival. Functional assays showed that HtrA3 overexpression enhanced CRC cell proliferation, migration, and invasion, while HtrA3 knockdown yielded opposite effects. In HtrA3-overexpressing HCT116 cells, increased phosphorylation of PI3K, AKT, and FOXO1 was observed, which was reduced upon treatment with the PI3K inhibitor LY294002. Conversely, in HtrA3-knockdown SW480 cells, these phosphorylation levels declined but were restored with the PI3K activator 740Y-P. In vivo, HtrA3 overexpression accelerated xenograft tumor growth. These findings suggest that HtrA3 promotes CRC cell proliferation, migration, and invasion, potentially involving PI3K-AKT-FOXO1 signaling, and support further investigation of HtrA3 as a potential prognostic biomarker and therapeutic target in CRC.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.",
    "Department of Epidemiology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.",
    "Fujian Provincial Key Laboratory for Zoonoses Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, Fujian, China.",
    "Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China.",
    "Department of General Surgery (Emergency Surgery), Fujian Medical University Union Hospital, Fuzhou, Fujian, China.",
    "Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jing Zheng",
      "orcid": "0000-0002-4321-0097"
    },
    {
      "affs": [
        0
      ],
      "name": "Silin Ren"
    },
    {
      "affs": [
        2
      ],
      "name": "Xianhua Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shutong Ren"
    },
    {
      "affs": [
        3
      ],
      "name": "Jinyan Chen",
      "orcid": "0000-0003-3743-2707"
    },
    {
      "affs": [
        4
      ],
      "name": "Dong Wang"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Xian-E Peng",
      "orcid": "0000-0002-4795-7956"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunli Wu",
      "orcid": "0000-0002-8478-2825"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2rpxpqvm4a4x1.bib",
  "cited_by": 0,
  "doi": "10.1002/cam4.72496",
  "fulltext_url": "https://europepmc.org/articles/PMC13744143",
  "id": "2rpxpqvm4a4x1",
  "issns": [
    "2045-7634"
  ],
  "landing_url": "https://europepmc.org/article/MED/42998026",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Protease and Inhibitor Mechanisms"
    ]
  ],
  "openalex": "W7225456761",
  "pdf_url": "https://europepmc.org/articles/PMC13744143?pdf=render",
  "pmcid": "PMC13744143",
  "pmid": "42998026",
  "published": "2026-11-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2rpxpqvm4a4x1.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42998026",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42998026"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Protease and Inhibitor Mechanisms",
      "subfield": "oncology"
    }
  ],
  "title": "HtrA3 Promotes Malignant Progression of Colorectal Cancer and Is Associated With PI3K-AKT-FOXO1 Signaling.",
  "title_text": "HtrA3 Promotes Malignant Progression of Colorectal Cancer and Is Associated With PI3K-AKT-FOXO1 Signaling.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T03:20:49Z",
  "url": "https://research.draconitic.com/paper/2rpxpqvm4a4x1",
  "venue": "Cancer medicine",
  "versions": []
}