Tissue-specific inflammation induces cell state plasticity with oncogenic addiction in mucosal melanoma
macrophages and their secretome. Maintenance of this inflammation-induced neural crest-like state in cancer cells depends on HER2 and HER3 activation. Inhibition of HER2/3 by pan-HER inhibitors blocks cell state plasticity and overcomes chemoresistance in primary MM cell lines and patient-derived xenograft (PDX) models. These findings provide insights into how the tissue of origin determines cancer aggressiveness, highlight the role of mucosal inflammation in driving melanoma stemness and chemoresistance, and advance the identification of effective treatment options currently lacking for patients with MM.
Authors
- A. Hunter Shain (ORCID: https://orcid.org/0000-0002-2999-9706)
- Yinan Chen
- Ruixin Liu (ORCID: https://orcid.org/0000-0002-8464-7033)
- Pengcong Hou (ORCID: https://orcid.org/0009-0001-4779-8801)
- Ronghui Xia (ORCID: https://orcid.org/0000-0002-6147-7174)
- Yanni Ma (ORCID: https://orcid.org/0009-0006-4985-5036)
- Hao Wang (ORCID: https://orcid.org/0000-0001-6881-9977)
- Qin Yang
- Hao Luo (ORCID: https://orcid.org/0000-0001-5415-7474)
- Xuhui Ma
- Robert L. Judson-Torres
- Ruixin Jiang
- Kaiyuan Hui
- Yupeng Zheng (ORCID: https://orcid.org/0000-0002-2165-7859)
- Wei Guo
- Min Jiang
- Meiling Hao
- Li Zhang
- Ming Lei
- Shengnan Zheng
- Jie Yang
- Hanlin Zeng
- Bin Jiang
- Guoxin Ren
- Xiaodong Jiang
- Xiaole Song
Institutions
- Xuzhou Medical College (CN)
- University of California, San Francisco (US)
- Shanghai Jiao Tong University (CN)
- University of Utah (US)
- Huntsman Cancer Institute (US)
- Soochow University (CN)
- Shanghai Stomatological Hospital (CN)
- Lianyungang Oriental Hospital (CN)
- Shanghai Ninth People's Hospital (CN)
- Eye & ENT Hospital of Fudan University (CN)
- Stomatology Hospital (CN)
- First Affiliated Hospital of Soochow University (CN)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1126/sciadv.ady4536
- Primary Topic
- Cutaneous Melanoma Detection and Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences