{
  "abstract": "Background: Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent non-melanoma skin cancer worldwide, with increasing incidence and considerable mortality following metastasis. Ras-associated binding protein 23 (Rab23) has been implicated in cSCC progression, but its molecular mechanisms remain incompletely understood. Methods: Rab23, Beclin1, and LC3-II protein expression was compared across human cSCC, actinic keratosis, and normal skin tissues. Rab23-dependent changes in autophagy-related markers, autophagic vacuoles, migration, invasion, and wound healing were investigated in oral SCC-derived Sa3 cells and cSCC models A431 and HSC-5. GTP dependence, responses to rapamycin and chloroquine, and AKT/mTOR and MEK/ERK1/2 signaling were assessed, including MEK1/2 inhibition with U0126. Public transcriptomic and spatial transcriptomic datasets were also analyzed. Results: Rab23 protein expression was significantly elevated in cSCC lesions compared with normal skin and actinic keratosis, accompanied by increased Beclin1 and LC3-II levels, and correlated positively with both markers. Rab23 overexpression increased Beclin1 and LC3-II expression and decreased p62 in a GTP-dependent manner. It also enhanced autophagic vacuole formation, migration, invasion, and wound healing. Rapamycin potentiated these effects, whereas chloroquine abrogated them. Rab23 activated both AKT/mTOR and MEK/ERK1/2 signaling; however, U0126 abolished Rab23-induced autophagy marker upregulation and migratory capacity. Transcriptomic and spatial transcriptomic analyses further supported the clinical relevance of the Rab23-ERK-autophagy axis in SCC aggressiveness. Conclusions: Rab23 promotes cSCC invasion, at least in part, through ERK-dependent autophagy enhancement, highlighting this signaling axis as a potential therapeutic target for cSCC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Surgery, the First Medical Center of Chinese People’s Liberation Army General Hospital, No. 28 Fuxing Road, Hai Dian District, Beijing 100853, China",
    "Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100080, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiaqiang Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziye Feng"
    },
    {
      "affs": [
        1
      ],
      "name": "Chunyu Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingrun Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/75e675f1z6y2q.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18213458",
  "fulltext_url": null,
  "id": "75e675f1z6y2q",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/21/3458",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7223810295",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/75e675f1z6y2q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18213458",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/21/3458"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Rab23 Drives Cutaneous Squamous Cell Carcinoma Invasion via ERK-Mediated Autophagy Activation",
  "title_text": "Rab23 Drives Cutaneous Squamous Cell Carcinoma Invasion via ERK-Mediated Autophagy Activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:58Z",
  "url": "https://research.draconitic.com/paper/75e675f1z6y2q",
  "venue": "Cancers",
  "versions": []
}