2. Academic Validation
  3. CAV2 promotes the invasion and metastasis of head and neck squamous cell carcinomas by regulating S100 proteins

CAV2 promotes the invasion and metastasis of head and neck squamous cell carcinomas by regulating S100 proteins

  • Cell Death Discov. 2022 Sep 16;8(1):386. doi: 10.1038/s41420-022-01176-1.
Yafei Wang  # 1 2 3,  Yun Wang  # 1 2 3,  Ruoyan Liu  # 3 4,  Chunli Wang 1 2 3,  Yi Luo 2 3,  Liwei Chen 2 3,  Yuchao He 2 3,  Keyun Zhu 2 3 5,  Hua Guo 6 7,  Ze Zhang 8 9,  Jingtao Luo 10 11
Affiliations

Affiliations

  • 1 Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
  • 2 Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 3 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • 4 Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
  • 5 Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 6 Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. guohua@tjmuch.com.
  • 7 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. guohua@tjmuch.com.
  • 8 Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. zhangze@tmu.edu.cn.
  • 9 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. zhangze@tmu.edu.cn.
  • 10 Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. jluo@tmu.edu.cn.
  • 11 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. jluo@tmu.edu.cn.
  • # Contributed equally.
PMID: 36114176 DOI: 10.1038/s41420-022-01176-1
Abstract

More than half of HNSCC patients are diagnosed with advanced disease. Locally advanced HNSCC is characterized by tumors with marked local invasion and evidence of metastasis to regional lymph nodes. CAV2 is a major coat protein of caveolins, important components of the plasma membrane. In this study, CAV2 was found to profoundly promote invasion and stimulate metastasis in vivo and in vitro. CAV2 was demonstrated to be a key regulator of S100 protein expression that upregulates the proteins levels of S100s, which promotes the invasion and migration and downregulates the expression of tumor suppressors. Mechanistically, CAV2 directly interacts with S100s in HNSCC cells, and CAV2 reduces S100A14 protein expression by promoting its ubiquitylation and subsequent degradation via the Proteasome. Moreover, we discovered that CAV2 promotes the interaction between S100A14 and the E3 ubiquitin Ligase TRIM29 and increases TRIM29 expression. Taken together, our findings indicate that CAV2 promotes HNSCC invasion and metastasis by regulating the expression of S100 proteins, presenting a novel potential target for Anticancer therapy in HNSCC.

Figures
Products