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AXL是人类结直肠癌中的一个癌靶标。

AXL is an oncotarget in human colorectal cancer.

作者信息

Martinelli Erika, Martini Giulia, Cardone Claudia, Troiani Teresa, Liguori Giuseppina, Vitagliano Donata, Napolitano Stefania, Morgillo Floriana, Rinaldi Barbara, Melillo Rosa Marina, Liotti Federica, Nappi Anna, Bianco Roberto, Berrino Liberato, Ciuffreda Loreta Pia, Ciardiello Davide, Iaffaioli Vincenzo, Botti Gerardo, Ferraiolo Fiorella, Ciardiello Fortunato

机构信息

Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.

Dipartimento di Patologia Diagnostica e di Laboratorio, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.

出版信息

Oncotarget. 2015 Sep 15;6(27):23281-96. doi: 10.18632/oncotarget.3962.

DOI:10.18632/oncotarget.3962
PMID:25966280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4695118/
Abstract

AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC.

摘要

AXL是一种由生长停滞特异性蛋白6（GAS6）激活的酪氨酸激酶受体，可调节癌细胞的增殖、迁移和血管生成。我们将AXL作为结直肠癌（CRC）的新治疗靶点进行了研究。在一组人CRC细胞系中评估了AXL和GAS6的表达及激活情况。用福瑞替尼进行AXL基因沉默或药物抑制可抑制CRC细胞的增殖、迁移和存活。在过表达AXL的人HCT116 CRC细胞的原位结肠模型中，福瑞替尼治疗可显著抑制肿瘤生长和腹膜转移扩散。在223例人CRC标本中，分别有76.7%和73.5%通过免疫组织化学（IHC）检测到AXL和GAS6过表达，这与低分化组织学分级相关。GAS6过表达与淋巴结受累和肿瘤分期有关。在146例CRC样本中有8例（5.4%）通过荧光原位杂交（FISH）发现AXL基因扩增。综上所述，抑制AXL可能代表CRC的一种新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/2f0347e1fbf5/oncotarget-06-23281-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/a7eed2ee1b0e/oncotarget-06-23281-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/9691d24f7fbf/oncotarget-06-23281-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/af0f96073971/oncotarget-06-23281-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/0ac121af3951/oncotarget-06-23281-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/518db6c359b9/oncotarget-06-23281-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/2f0347e1fbf5/oncotarget-06-23281-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/a7eed2ee1b0e/oncotarget-06-23281-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/9691d24f7fbf/oncotarget-06-23281-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/af0f96073971/oncotarget-06-23281-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/0ac121af3951/oncotarget-06-23281-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/518db6c359b9/oncotarget-06-23281-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e1b/4695118/2f0347e1fbf5/oncotarget-06-23281-g006.jpg

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Oncotarget. 2015 Apr 30;6(12):10146-60. doi: 10.18632/oncotarget.3380.
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Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer.氟尿嘧啶、亚叶酸钙和伊立替康联合西妥昔单抗治疗与结直肠癌的 RAS 突变。
J Clin Oncol. 2015 Mar 1;33(7):692-700. doi: 10.1200/JCO.2014.59.4812. Epub 2015 Jan 20.
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The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma.
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MedComm (2020). 2023 Dec 7;4(6):e446. doi: 10.1002/mco2.446. eCollection 2023 Dec.
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An Activated Dendritic-Cell-Related Gene Signature Indicative of Disease Prognosis and Chemotherapy and Immunotherapy Response in Colon Cancer Patients.活化的树突状细胞相关基因特征可预测结肠癌患者的疾病预后和化疗及免疫治疗反应。
Int J Mol Sci. 2023 Nov 3;24(21):15959. doi: 10.3390/ijms242115959.
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