一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cell Communication and Signaling >>article
Cell Communication and Signaling

Cell Communication and Signaling

IF: 8.2
Download PDF

Targeting autophagy in HCC treatment: exploiting the CD147 internalization pathway

Published:3 December 2024 DOI: 10.1186/s12964-024-01956-5 PMID: 39627812
Meirui Qian,?Ziyu Wan,?Xue Liang,?Lin Jing,?Huijie Zhang,?Heyao Qin,?Wenli Duan,?Ruo Chen,?Tianjiao Zhang,?Qian He,?Meng Lu,?Jianli Jiang

Abstract

Background/aims: Chemotherapy resistance in liver cancer is a major clinical issue, with CD147 playing a vital role in this process. However, the specific mechanisms underlying these processes remain largely unknown. This study investigates how CD147 internalization leads to cytoprotective autophagy, contributing to chemotherapy resistance in hepatocellular carcinoma (HCC).

Methods: Utilizing bioinformatics methods for KEGG pathways enrichment and screening key molecules associated with chemotherapy resistance through?analyses of GEO and TCGA databases. An overexpression/knockdown system was used to study how CD147 internalization leads to autophagy in vitro and in vivo. The process was observed using microscopes, and molecular interactions and autophagy flux were analyzed. Analyzing the internalization of CD147 intracellular domains and the interaction with G3BP1 in clinical chemotherapy recurrence HCC tissues by immunohistochemistry, tissue immunofluorescence, and mass spectrometry. A tumor xenograft mice model was used to study cytoprotective autophagy induced by CD147 and test the effectiveness of combining cisplatin with an autophagy inhibitor in nude mice models.

Results: In our study,?we identified the tumor-associated membrane protein CD147, which implicated?in chemoresistance lysosome pathways, by evaluating its protein degree value and betweenness centrality using Cytoscape. Our findings revealed that CD147?undergoes internalization and interacts with G3BP1 following treatment with cisplatin and methyl-β-cyclodextrin, forming a complex?that is transported to lysosomes via Rab7A. Notably, higher doses of cisplatin enhanced CD147-mediated lysosomal transport while concurrently inhibiting SG assembly. The CD147-G3BP1 complex additionally inhibits mTOR activity, promoting autophagy and augmenting chemoresistance in hepatoma cells. In vivo studies investigations and analyses of clinical samples revealed that elevated internalization of CD147 is associated with chemotherapy recurrence in liver cancer and the maintenance of stem cells. Mice experiments found that the?combined?administration of cisplatin and hydroxychloroquine enhanced the efficacy of treatment.

Conclusions: This study reveals that CD147 internalization and CD147-G3BP1 complex translocation to lysosomes induce cytoprotective autophagy, reducing chemotherapy sensitivity by suppressing mTOR activity. It is also shown that chemotherapy drugs combined with autophagy inhibitors can improve the therapeutic effect of cancer, providing new insights into potential targeted therapeutic approaches in treating HCC.

Similar articles

IF:7.1

Itaconic acid ameliorates necrotizing enterocolitis through the TFEB-mediated autophagy-lysosomal pathway

Free Radical Biology and Medicine Baozhu Chen, Yufeng Liu,etc Published: 19 November 2024
IF:3.2

PKN2 Promotes Peripheral Nerve Repair by Regulating Autophagy via Activation of the AKT‐mTOR Pathway: An In Vitro Study

Journal of Biochemical and Molecular Toxicology Lin Wang, Yuan‐sheng Huang,etc Published: 22 November 2024
聂拉木县| 抚松县| 彰化县| 清苑县| 从化市| 嘉黎县| 玉门市| 大同县| 白河县| 武隆县| 石渠县| 无锡市| 昌都县| 汤原县| 灌阳县| 英吉沙县| 鹤山市| 济宁市| 赫章县| 泗阳县| 土默特右旗| 桦甸市| 乐山市| 博兴县| 浪卡子县| 武邑县| 隆尧县| 洪洞县| 博客| 邵武市| 高青县| 霍林郭勒市| 周口市| 恩平市| 松阳县| 伊春市| 乌鲁木齐市| 铁岭市| 肇庆市| 微博| 枣阳市|