2. Academic Validation
  3. ALIX promotes cell migration and invasion of head and neck squamous cell carcinoma by regulating the expression of MMP9, MMP14, VEGF-C

ALIX promotes cell migration and invasion of head and neck squamous cell carcinoma by regulating the expression of MMP9, MMP14, VEGF-C

  • Arch Oral Biol. 2023 Jul:151:105696. doi: 10.1016/j.archoralbio.2023.105696.
Qi-Hui Xie 1,  Wei-Ming Wang 2,  Jie-Gang Yang 1,  Hou-Fu Xia 1,  Bo-Lin Xiao 3,  Gao-Hong Chen 3,  Jue Huang 3,  Rui-Fang Li 4,  Gang Chen 5
Affiliations

Affiliations

  • 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 2 Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • 3 The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 4 The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: [email protected].
  • 5 The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China; TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China. Electronic address: [email protected].
PMID: 37086494 DOI: 10.1016/j.archoralbio.2023.105696
Abstract

Objective: The poor survival rate of head and neck squamous cell carcinoma (HNSCC), one of the most prevalent human Cancer, is attributed to frequent locoregional recurrence and lymph node metastases. Though it is reported that the expression of ALG-2 interacting protein X (ALIX) closely correlates with the progression of various tumors, its role in HNSCC remains unclear. The present study aims to investigate the role of ALIX in the development of HNSCC.

Design: With immunohistochemical staining, the expression levels of ALIX and series of related functional proteins were compared in normal mucosal (n = 18), HNSCC tissues (n = 54), and metastatic lymph nodes (n = 11). Further, the correlation analysis was performed among the proteins detected. By knocking down ALIX in HNSCC cell lines, the correlation of ALIX with the proteins was verified in vitro. The role of ALIX in proliferation, migration, and invasion of HNSCC cells was further studied by flow cytometry, wounding healing, and transwell assays, respectively.

Results: Higher expression level of ALIX was revealed in HNSCC samples, especially in metastatic lymph nodes, than in normal mucosal tissues. Accordingly, increasing levels of MMP9, MMP14, and VEGF-C were also discovered in metastatic lymph nodes and significantly correlated with the expression of ALIX. In vitro assays demonstrated that the knockdown of ALIX reduced both the transcriptional and protein levels of MMP9, MMP14, and VEGF-C, together with suppressed migration and weakened invasion of HNSCC cell lines.

Conclusions: ALIX up-regulated the expression of MMP9, MMP14 and VEGF-C, and promoted migration and invasion of HNSCC cells.

Keywords

Lymphatic metastasis; Matrix metalloproteinases; PDCD6IP Protein; Squamous cell carcinoma of head and neck; Vascular endothelial growth factor C.

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