2. Academic Validation
  3. Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma

Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma

  • Cell Death Dis. 2022 Feb 17;13(2):158. doi: 10.1038/s41419-022-04610-5.
Zihang Ling  # 1 2,  Wei Li  # 1 2,  Jiaqi Hu  # 1 2,  Yuanyuan Li 1 2,  Miao Deng 1 2,  Siyuan Zhang 1 2,  Xianyue Ren 1 2,  Tong Wu 1 2,  Juan Xia 3 4,  Bin Cheng 5 6,  Xiaoan Tao 7 8
Affiliations

Affiliations

  • 1 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, P. R. China.
  • 2 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, 510055, P. R. China.
  • 3 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, P. R. China. xiajuan@mail.sysu.edu.cn.
  • 4 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, 510055, P. R. China. xiajuan@mail.sysu.edu.cn.
  • 5 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, P. R. China. chengbin@mail.sysu.edu.cn.
  • 6 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, 510055, P. R. China. chengbin@mail.sysu.edu.cn.
  • 7 Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, P. R. China. taoxiaoa@mail.sysu.edu.cn.
  • 8 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, 510055, P. R. China. taoxiaoa@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 35177591 DOI: 10.1038/s41419-022-04610-5
Abstract

For head and neck squamous cell carcinoma (HNSCC), the local invasion and distant metastasis represent the predominant causes of mortality. Targeted inhibition of chemokines and their receptors is an ongoing antitumor strategy established on the crucial roles of chemokines in Cancer invasion and metastasis. Herein, we showed that C-C motif chemokine ligand 2 (CCL2)- C-C motif Chemokine Receptor 4 (CCR4) signaling, but not the CCL2- C-C motif Chemokine Receptor 2 (CCR2) axis, induces the formation of the vav guanine nucleotide exchange factor 2 (Vav2)- Rac family small GTPase 1 (Rac1) complex to activate the phosphorylation of Myosin light chain (MLC), which is involved in the regulation of cell motility and Cancer metastasis. We identified that targeting CCR4 could effectively interrupt the activation of HNSCC invasion and metastasis induced by CCL2 without the promoting Cancer relapse observed during the subsequent withdrawal period. All current findings suggested that CCL2-CCR4-Vav2-Rac1-p-MLC signaling plays an essential role in cell migration and Cancer metastasis of HNSCC, and CCR4 may serve as a new potential molecular target for HNSCC therapy.

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