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Published on: January 26, 2024
ANXA6/TRPV2 axis promotes lymphatic metastasis in head and neck squamous cell carcinoma by inducing autophagy
Min Wang1, Min Pan1, Yanshi Li1
1Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Background:
Head and neck squamous cell carcinoma (HNSCC) is highly aggressive with a significant tropism of lymph nodes, which restricts treatment options and negatively impacts patient outcomes. Although progress has been made in understanding the molecular mechanisms underlying lymphatic metastasis (LM), these mechanisms remain elusive. ANXA6 is a scaffold protein that participates in tumor pathogenesis and autophagy regulation; however, how ANXA6 affects autophagy and LM in HNSCC cells remains unknown.
Methods:
RNA sequencing was performed on HNSCC clinical specimens with or without metastasis as well as on The Cancer Genome Atlas dataset to investigate ANXA6 expression and survival. Both in vitro and in vivo studies were performed to investigate the role of ANXA6 in the regulation of LM in HNSCC. The molecular mechanism by which ANXA6 interacts with TRPV2 was examined at the molecular level.
Results:
ANXA6 expression was significantly upregulated in HNSCC patients with LM and higher expression was associated with poor prognosis. ANXA6 overexpression promoted the proliferation and mobility of FaDu and SCC15 cells in vitro; however, ANXA6 knockdown retarded LM in HNSCC in vivo. ANXA6 induced autophagy by inhibiting the AKT/mTOR signaling pathway in HNSCC, thereby regulating the metastatic capability of the disease. Furthermore, ANXA6 expression positively correlated with TRPV2 expression both in vitro and in vivo. Lastly, TRPV2 inhibition reversed ANXA6-induced autophagy and LM.
Conclusions:
These results indicate that the ANXA6/TRPV2 axis facilitates LM in HNSCC by stimulating autophagy. This study provides a theoretical basis for investigating the ANXA6/TRPV2 axis as a potential target for the treatment of HNSCC, as well as a biomarker for predicting LM.
Insights
The ANXA6/TRPV2 axis promotes head and neck squamous cell carcinoma (HNSCC) lymphatic metastasis by stimulating autophagy. Targeting this axis may offer new therapeutic strategies and biomarkers for HNSCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is aggressive, with frequent lymph node metastasis, limiting treatment and worsening outcomes.
- While molecular mechanisms of lymphatic metastasis (LM) in HNSCC are studied, they remain incompletely understood.
- The role of ANXA6, a scaffold protein involved in tumor pathogenesis and autophagy, in HNSCC lymphatic metastasis is unknown.
Purpose of the Study:
- To investigate the role of ANXA6 in regulating lymphatic metastasis (LM) in head and neck squamous cell carcinoma (HNSCC).
- To elucidate the molecular mechanisms underlying ANXA6-mediated autophagy and LM in HNSCC.
- To explore the potential of the ANXA6/TRPV2 axis as a therapeutic target and biomarker for HNSCC.
Main Methods:
- RNA sequencing of HNSCC clinical specimens and The Cancer Genome Atlas (TCGA) data to analyze ANXA6 expression and survival.
- In vitro (FaDu, SCC15 cells) and in vivo studies to assess the impact of ANXA6 on proliferation, mobility, and LM.
- Molecular analysis to examine the interaction between ANXA6 and TRPV2 and its effect on autophagy and LM.
Main Results:
- ANXA6 expression is significantly upregulated in HNSCC with LM and correlates with poor prognosis.
- ANXA6 overexpression enhances HNSCC cell proliferation and mobility in vitro; ANXA6 knockdown inhibits LM in vivo.
- ANXA6 induces autophagy by inhibiting the AKT/mTOR pathway, thereby regulating HNSCC metastatic capability.
- ANXA6 expression positively correlates with TRPV2 expression; TRPV2 inhibition reverses ANXA6-induced autophagy and LM.
Conclusions:
- The ANXA6/TRPV2 axis promotes LM in HNSCC by stimulating autophagy.
- This axis represents a potential therapeutic target for HNSCC treatment.
- The ANXA6/TRPV2 axis may serve as a predictive biomarker for LM in HNSCC.
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