TBC1D14 inhibits autophagy to suppress lymph node metastasis in head and neck squamous cell carcinoma by downregulating macrophage erythroblast attacher

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

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

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

来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000775177900002

JCR分区：Q1

影响因子：9.2

年份：2022

卷号：18

期号：5

开始页：1795

结束页：1812

文献类型：Article

关键词：  head and neck squamous cell carcinoma; lymph node metastasis; macrophage erythroblast attacher; autophagy

摘要："Aims: This study aimed to identify the correlation and molecular mechanism between TBC1 domain family member 14 (TBC1D14) and lymph node metastasis (LNM) in head and neck squamous cell carcinoma Methods: Whole transcriptome sequencing of HNSCC tissues with or without LNM was performed. TBC1D14 expression was quantified in HNSCC tissues. The role of TBC1D14 in HNSCC migration, invasion, autophagy, and LNM was investigated by wound healing, Transwell, western blotting, immunofluorescence, and transmission electron microscopy assays in vitro and in a mouse model in vivo. The correlation between autophagy and LNM was detected by wound healing and Transwell assays in vitro and western blotting in vivo. Mass spectrometry was used to identify the downstream target proteins. The correlation between TBC1D14 expression and macrophage erythroblast attacher (MAEA) expression was identified by qRT-PCR and western blotting assays in vitro and immunohistochemistry in vivo. The gain-of-function strategy was applied to further reveal the role of MAEA in the TBC1D14-induced autophagy of HNSCC cells. Results: TBC1D14 was a co-differentially expressed gene in the sequencing results, The Cancer Genome Atlas Data Portal, and Gene Expression Omnibus databases. TBC1D14 had a lower RNA and protein expression in HNSCC with LNM samples and was a favorable prognostic indicator. TBC1D14 inhibited the migration and invasion of HNSCC in vivo. Mechanistically, TBC1D14-induced autophagy suppression inhibited the migration and invasion of HNSCC. TBC1D14 expression negatively correlated with MAEA expression both in vitro and in vivo. Furthermore, MAEA overexpression could reverse TBC1D14-induced autophagy suppression. Conclusion: TBC1D14 is a novel LNM inhibitor in HNSCC and a favorable prognostic marker. TBC1D14 suppresses autophagy to inhibit LNM in HNSCC by downregulating MAEA expression. The results clarify the molecular mechanism of TBC1D14 in HNSCC."

基金机构：National Natural Science Foundation of China [82103145]; China Postdoctoral Science Foundation [2020M68 3635XB]; Technology Innovation and Application special Project of Chongqing Science and Technology Bureau [cstc2019jscx-msxm0545]

基金资助正文："This study was supported by National Natural Science Foundation of China (No. 82103145), China Postdoctoral Science Foundation (No. 2020M68 3635XB) and Technology Innovation and Application special Project of Chongqing Science and Technology Bureau (No. cstc2019jscx-msxm0545)."