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EPLIN是一种潜在的致癌分子，对胰腺癌的生长、迁移和耐药性有影响。

EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer.

作者信息

Zeng Jianyuan, Wang Cai, Ruge Fiona, Ji Edison Ke, Martin Tracey A, Sanders Andrew J, Jia Shuqin, Hao Chunyi, Jiang Wen G

机构信息

School of Medicine, Cardiff University, Henry Wellcome Building, Cardiff, CF14 4XN, UK.

Gastrointestinal Cancer Centre, Peking University Cancer Hospital, Peking University, Fucheng Road, Haidian District, Beijing, China.

出版信息

Sci Rep. 2024 Dec 28;14(1):30850. doi: 10.1038/s41598-024-81485-w.

DOI:10.1038/s41598-024-81485-w
PMID:39730634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11680852/
Abstract

Most pancreatic cancer patients are diagnosed at advanced stages, with poor survival rates and drug resistance making pancreatic cancer one of the highest causes of cancer death in the UK. Understanding the underlying mechanism behind its carcinogenesis, metastasis and drug resistance has become an essential task for researchers. We have discovered that a well-established tumour suppressor, EPLIN, has an oncogenic rather than suppressive role in pancreatic cancer. Notably, upregulation of EPLIN was observed in pancreatic cancer samples compared to normal samples at RNA and protein levels. Moreover, the presence of EPLIN resulted in poor clinical outcomes in patients. We also report that inhibition of EPLIN led to reduced cellular growth and migration in pancreatic cancer cells. EPLIN regulates expression and phosphorylation levels of several key players in MAPK and PIK3CA-AKT signalling pathways, as well as key contributors of EMT. Furthermore, EPLIN mediates the inhibitory ability PIK3 kinases, MEK and ERK inhibitors have on cell migration. EPLIN was also found to have an impact on pancreatic cancer cells response to chemotherapeutic and EGFR/HER2 targeted therapeutic agents, namely gemcitabine, fluorouracil (5FU) and neratinib (Nerlynx).

摘要

大多数胰腺癌患者在晚期才被诊断出来，生存率低且具有耐药性，这使得胰腺癌成为英国癌症死亡的主要原因之一。了解其致癌、转移和耐药背后的潜在机制已成为研究人员的一项重要任务。我们发现，一种已被充分证实的肿瘤抑制因子EPLIN在胰腺癌中具有致癌而非抑制作用。值得注意的是，与正常样本相比，在RNA和蛋白质水平上，胰腺癌样本中EPLIN的表达上调。此外，EPLIN的存在导致患者临床预后不良。我们还报告称，抑制EPLIN会导致胰腺癌细胞的生长和迁移减少。EPLIN调节MAPK和PIK3CA-AKT信号通路中几个关键分子的表达和磷酸化水平，以及EMT的关键促成因素。此外，EPLIN介导PIK3激酶、MEK和ERK抑制剂对细胞迁移的抑制能力。还发现EPLIN对胰腺癌细胞对化疗药物和EGFR/HER2靶向治疗药物（即吉西他滨、氟尿嘧啶（5FU）和来那替尼（Nerlynx））的反应有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/2d2f9426b135/41598_2024_81485_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/bffe73c9809f/41598_2024_81485_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/9b318880ae33/41598_2024_81485_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/5b596cfde9f5/41598_2024_81485_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/344f122a48e3/41598_2024_81485_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/9d079f9c961e/41598_2024_81485_Fig5a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/185d69d5baf6/41598_2024_81485_Fig5b_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/0489e0b9c03c/41598_2024_81485_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/dedb70f275d4/41598_2024_81485_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/2d2f9426b135/41598_2024_81485_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/bffe73c9809f/41598_2024_81485_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/9b318880ae33/41598_2024_81485_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/5b596cfde9f5/41598_2024_81485_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/344f122a48e3/41598_2024_81485_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/9d079f9c961e/41598_2024_81485_Fig5a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/185d69d5baf6/41598_2024_81485_Fig5b_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/0489e0b9c03c/41598_2024_81485_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/dedb70f275d4/41598_2024_81485_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/236e/11680852/2d2f9426b135/41598_2024_81485_Fig10_HTML.jpg

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Exp Cell Res. 2024 Feb 1;435(1):113910. doi: 10.1016/j.yexcr.2023.113910. Epub 2024 Jan 5.
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EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration.EPLIN-β 是鸟氨酸脱羧酶抗酶 1 的一种新型底物，介导细胞迁移。
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在胰腺癌细胞对 MEK 和 PI3K 激酶抑制的适应性耐药中，蛋白质组学特征和潜在的药理学机会。
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EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance.EPLIN，结直肠癌中的一种假定肿瘤抑制因子，与耐药性的关系。
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Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer.靶向胰腺癌中 PI3K/AKT/mTOR 通路的前景。
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