ANXA6/TRPV2 axis promotes lymphatic metastasis in head and neck squamous cell carcinoma by inducing autophagy

作者全名："Wang, Min; Pan, Min; Li, Yanshi; Lu, Tao; Wang, Zhihai; Liu, Chuan; Hu, Guohua"

作者地址："[Wang, Min; Pan, Min; Li, Yanshi; Lu, Tao; Wang, Zhihai; Liu, Chuan; Hu, Guohua] Chongqing Med Univ, Dept Otorhinolaryngol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Hu, GH (通讯作者)，Chongqing Med Univ, Dept Otorhinolaryngol, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：EXPERIMENTAL HEMATOLOGY & ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000980937200001

JCR分区：Q1

影响因子：9.4

年份：2023

卷号：12

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：ANXA6; TRPV2; Head and neck squamous cell carcinoma; Autophagy; Lymphatic metastasis

摘要："BackgroundHead 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.MethodsRNA 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.ResultsANXA6 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.ConclusionsThese 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."

基金机构："National Natural Science Foundation of China [82173303, 82103145, 81902776]; Natural Science Foundation of Chongqing [cstc2021ycjh-bgzxm0149]; China Postdoctoral Science Foundation [2020TQ0394, 2022MD723737]; Chongqing Postdoctoral Research Special Funding Project [2021XM3029]; Joint Science and Health Project of Chongqing [2020FYYX221]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 82173303, 82103145, 81902776), Natural Science Foundation of Chongqing (No. cstc2021ycjh-bgzxm0149), China Postdoctoral Science Foundation (No. 2020TQ0394, 2022MD723737), Chongqing Postdoctoral Research Special Funding Project (No. 2021XM3029), and the Joint Science and Health Project of Chongqing (No. 2020FYYX221)."