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Published on: June 7, 2019
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CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
Xu Zhang1,2, Yeye Guo1,2, Ta Xiao3
1Department of Dermatology, Xiangya Hospital, Central South University; Hunan Key Laboratory of Skin Cancer and Psoriasis and Hunan Engineering Research Center of Skin Health and Disease; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Xiangya Road #87, Changsha, 410008, Hunan, China.
Journal of Experimental & Clinical Cancer Research : CR
|August 13, 2022
Summary
CD147 overexpression in the epidermis drives skin cancer by activating keratinocytes and recruiting myeloid-derived suppressor cells (MDSCs). This occurs through the RSK2/AP-1 pathway, highlighting CD147 as a potential therapeutic target for cutaneous squamous-cell carcinoma (cSCC).
Area of Science:
- Dermatology and Oncology
- Molecular Biology and Cancer Research
Background:
- Cutaneous squamous-cell carcinoma (cSCC) pathogenesis involves epidermal malignant transformation.
- CD147's role in epidermal malignant transformation in vivo is not well understood, despite its known involvement in other cancers.
Purpose of the Study:
- To investigate the role of CD147 in epidermal malignant transformation and tumorigenesis in vivo.
- To elucidate the molecular mechanisms by which CD147 influences keratinocyte activation and immune cell recruitment.
Main Methods:
- Generation of epidermal CD147-overexpressing (EpiCD147-OE) and knockout (EpiCD147-KO) transgenic mouse models.
- RNA-sequencing, q-PCR, immunohistochemistry, and flow cytometry for gene expression and cell analysis.
- Biochemical assays (immunoprecipitation, EMSA, ChIP) to determine the CD147 interaction and signaling pathway.
Main Results:
- Epidermal CD147 overexpression induced spontaneous tumor formation and accelerated tumorigenesis in a mouse model.
- CD147 overexpression upregulated chemokines (e.g., CXCL1), increasing myeloid-derived suppressor cell (MDSC) infiltration.
- CD147 interacts with RSK2, activating the RSK2/AP-1 pathway, which promotes CXCL1 expression and contributes to malignant transformation.
Conclusions:
- CD147 plays a critical role in epidermal malignant transformation in vivo.
- The RSK2/AP-1 signaling pathway mediates CD147's effects on keratinocyte activation and MDSC recruitment.
- Targeting CD147 may offer a therapeutic strategy for cSCC.
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