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竞争性结合G3BPs并激活mTORC1以增强HER2阳性乳腺癌对曲妥珠单抗的耐受性。

competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance.

作者信息

He Yaozhou, Liu Yincheng, Gong Jue, Yang Fan, Sun Chunxiao, Yan Xueqi, Duan Ningjun, Hua Yijia, Zeng Tianyu, Fu Ziyi, Liang Yan, Li Wei, Huang Xiang, Tang Jinhai, Yin Yongmei

机构信息

Department of Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China.

Department of General Surgery, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China.

出版信息

Int J Biol Sci. 2024 Jul 15;20(10):3923-3941. doi: 10.7150/ijbs.87415. eCollection 2024.

DOI:10.7150/ijbs.87415
PMID:39113695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11302882/
Abstract

About 20% of breast cancer patients are positive for HER2. The efficacy of current treatments is limited by primary and secondary resistance to trastuzumab. tRNA-derived fragments (tRFs) have shown crucial regulatory roles in various cancers. This study aimed to evaluate the role of in regulating the resistance of HER2-positive breast cancer against trastuzumab. was highly expressed in trastuzumab-resistant cells, and its expression level could predict the resistance to trastuzumab. High expression of promoted the growth and proliferation of trastuzumab-exposed cells. RNA-pulldown assay and mass spectrometry were performed to identify Ras GTPase-activating protein-binding proteins 1 and 2 (G3BPs) (two proteins targeted by ); RNA-immunoprecipitation (RIP) to confirm their bindings; co-immunoprecipitation (co-IP) and RNA-pulldown assay to determine the binding domains between G3BPs and . bound to the nuclear transport factor 2 like domain(NTF2 domain) of G3BPs through a specific sequence. relied on G3BPs and NTF2 domain to increase trastuzumab tolerance. competed with lysosomal associated membrane protein 1(LAMP1) for NTF2 domain, thereby inhibiting lysosomal localization of G3BPs and tuberous sclerosis complex (TSC). Overexpression of inhibited phosphorylation of TSCs and promoted the activation of mechanistic target of rapamycin complex 1(MTORC1) to enhance cell proliferation and entice the resistance of HER2-positive breast cancer against trastuzumab.

摘要

约20%的乳腺癌患者HER2呈阳性。目前治疗的疗效受到对曲妥珠单抗原发性和继发性耐药的限制。tRNA衍生片段（tRFs）在多种癌症中发挥着关键的调控作用。本研究旨在评估[未提及的物质]在调节HER2阳性乳腺癌对曲妥珠单抗耐药性中的作用。[未提及的物质]在曲妥珠单抗耐药细胞中高表达，其表达水平可预测对曲妥珠单抗的耐药性。[未提及的物质]的高表达促进了暴露于曲妥珠单抗的细胞的生长和增殖。进行RNA下拉试验和质谱分析以鉴定Ras GTP酶激活蛋白结合蛋白1和2（G3BPs）（[未提及的物质]靶向的两种蛋白质）；进行RNA免疫沉淀（RIP）以确认它们的结合；进行免疫共沉淀（co-IP）和RNA下拉试验以确定G3BPs与[未提及的物质]之间的结合结构域。[未提及的物质]通过特定序列与G3BPs的核转运因子2样结构域（NTF2结构域）结合。[未提及的物质]依赖G3BPs和NTF2结构域来增加曲妥珠单抗耐受性。[未提及的物质]与溶酶体相关膜蛋白1（LAMP1）竞争NTF2结构域，从而抑制G3BPs和结节性硬化复合物（TSC）的溶酶体定位。[未提及的物质]的过表达抑制了TSC的磷酸化并促进了雷帕霉素复合物1（MTORC1）机制靶点的激活，以增强细胞增殖并诱使HER2阳性乳腺癌对曲妥珠单抗产生耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/43fb7c819923/ijbsv20p3923g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/c568af7b09ad/ijbsv20p3923g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/2ff53c1de09f/ijbsv20p3923g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/bae4a6e11692/ijbsv20p3923g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/efa331e535ae/ijbsv20p3923g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/c2f5418e3271/ijbsv20p3923g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/ba3937e6786e/ijbsv20p3923g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/dc15fcf697bc/ijbsv20p3923g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/43fb7c819923/ijbsv20p3923g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/c568af7b09ad/ijbsv20p3923g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/2ff53c1de09f/ijbsv20p3923g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/bae4a6e11692/ijbsv20p3923g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/e3e2cdf6f6b1/ijbsv20p3923g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/efa331e535ae/ijbsv20p3923g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/c2f5418e3271/ijbsv20p3923g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/ba3937e6786e/ijbsv20p3923g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/dc15fcf697bc/ijbsv20p3923g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d53/11302882/43fb7c819923/ijbsv20p3923g009.jpg

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2
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3
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Cancers (Basel). 2024 Mar 11;16(6):1118. doi: 10.3390/cancers16061118.
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Mol Cancer. 2022 Dec 13;21(1):217. doi: 10.1186/s12943-022-01686-7.
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