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p62-mTORC1与表皮生长因子受体（EGFR）信号通路的相互作用促进口腔癌顺铂耐药。

Interplay of p62-mTORC1 and EGFR signaling promotes cisplatin resistance in oral cancer.

作者信息

Chang Hsiu-Chuan, Yang Cheng-Chieh, Loi Lai-Keng, Hung Chi-Hsun, Wu Cheng-Hsien, Lin Yu-Cheng

机构信息

Institute of Oral Biology, School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Department of Dentistry, School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

Heliyon. 2024 Mar 21;10(6):e28406. doi: 10.1016/j.heliyon.2024.e28406. eCollection 2024 Mar 30.

DOI:10.1016/j.heliyon.2024.e28406
PMID:38560690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10979205/
Abstract

Cisplatin resistance poses a major challenge in the treatment of oral squamous cell carcinoma (OSCC). Deeper investigations into the mechanisms underlying this drug resistance is of great importance. Here, we used cellular assays and clinical immunohistochemistry to examine molecular pathways involved in both innate and acquired cisplatin resistance. We demonstrated that the p62-mTORC1 signaling complex plays a pivotal role, and is driven by the EGFR signaling network, specifically through the PI3K-Akt axis and the transcription factor C/EBP-β. Elevated -mTOR expression was associated with cancer relapse and poor prognosis among oral cancer patients. Additionally, we illustrated that mTOR inhibitors enhance the cytotoxic effect of cisplatin, by employing cancer stem cell characteristics. Our work unveils fundamental mechanisms for cisplatin resistance, thereby presenting therapeutic implications for OSCC.

摘要

顺铂耐药是口腔鳞状细胞癌（OSCC）治疗中的一个重大挑战。深入研究这种耐药性的潜在机制非常重要。在此，我们使用细胞实验和临床免疫组织化学来研究先天性和获得性顺铂耐药所涉及的分子途径。我们证明p62-mTORC1信号复合物起关键作用，并且由EGFR信号网络驱动，特别是通过PI3K-Akt轴和转录因子C/EBP-β。mTOR表达升高与口腔癌患者的癌症复发和预后不良相关。此外，我们还表明mTOR抑制剂通过利用癌症干细胞特性增强了顺铂的细胞毒性作用。我们的工作揭示了顺铂耐药的基本机制，从而为OSCC提供了治疗意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/dc337919c5c7/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/3e4ea510fb63/ga1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/bb0f6faebe2d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/8a031ea27158/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/fdc2d07e9506/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/1623922ac8ec/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/8328a7365a91/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/dc337919c5c7/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/3e4ea510fb63/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/e8f9c28902d0/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/bb0f6faebe2d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/8a031ea27158/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/fdc2d07e9506/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/1623922ac8ec/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/8328a7365a91/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61a1/10979205/dc337919c5c7/gr7.jpg

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SP110 Could be Used as a Potential Predictive and Therapeutic Biomarker for Oral Cancer.SP110可作为口腔癌潜在的预测和治疗生物标志物。
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