Peak1-flox 基因敲除小鼠

下单100%中奖,最高可得千元京东卡
复苏/繁育服务
产品名称

Peak1-flox 基因敲除小鼠

产品编号

S-CKO-08643

品系全称

C57BL/6JCya-Peak1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-244895-Peak1-B6J-VA

品系状态

使用本品系发表的文献需注明: Peak1-flox 基因敲除小鼠 mice (Strain S-CKO-08643) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
pseudopodium-enriched atypical kinase 1
基因别称
1110049L02Rik,9530046P14,C230081A13Rik,SGK269,mKIAA2002
染色体号
Chr 9 (Mouse)
转录本 ID
NCBI: NM_172924 | Ensembl: ENSMUST00000061552
修饰方式
条件性基因敲除
靶向范围
Exon 4
敲除长度
~3.7 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:2442366Mice homozygous for a null allele exhibit reduced angiogenesis in postnatal retina, VEGFA-treated aortas, and transplanted breast cancer cells infected with VEGFA-expressing adenovirus.
PEAK1,也称为Pseudopodium-enriched atypical kinase 1,是一种非受体酪氨酸激酶。它在细胞骨架和伪足中丰富,并在细胞迁移和增殖中发挥重要作用。PEAK1在多种人类恶性肿瘤中过度表达,与肿瘤侵袭、转移和化疗耐药性相关。此外,PEAK1还在血管生成、细胞分化和信号传导中发挥作用。

在乳腺癌中,PEAK1的表达与肿瘤大小、分级、分期、淋巴结转移、复发、Ki-67表达和Her-2表达相关。抑制PEAK1可以降低细胞生长、侵袭和转移,并逆转乳腺癌细胞对多柔比星的耐药性[1]。PEAK1作为分子开关,调节TGFβ信号通路,促进肿瘤进展和转移[3]。PEAK1激活JAK/STAT3信号通路,促进黑色素瘤细胞的生长、侵袭和转移[4]。

在结直肠癌中,PEAK1的表达与肿瘤大小、分化状态、转移和临床分期相关。PEAK1过表达抑制结直肠癌细胞生长、侵袭和转移,而敲除PEAK1则产生相反的效果。PEAK1-PPP1R12B轴通过调节Grb2/PI3K/Akt信号通路抑制结直肠癌的发生和转移[5]。

在甲状腺癌中,PEAK1的过度表达与肿瘤细胞存活和化疗耐药性相关。抑制PEAK1可以降低细胞活力和集落形成,但不影响细胞凋亡。抑制PEAK1可以增强8505C和Hth74细胞对vemurafenib的敏感性,通过诱导细胞凋亡来降低细胞活力[6]。

在前列腺癌中,PEAK1的表达与MRI定义的低氧水平相关。在中等/严重低氧水平下,PEAK1表达上调,反映了MYC的上调和高Ki67增殖指数。PEAK1基因表达程序与细胞增殖相关,可能是干预的候选靶点[2]。

在结直肠癌中,PEAK1的表达与EGFR/KRas信号通路和miR-181d相关。沉默PEAK1可以抑制细胞增殖、迁移和侵袭,并抑制肿瘤异种移植的生长。PEAK1被EGFR信号通路诱导,并需要KRas诱导的结直肠癌细胞生长和转移[7]。

在乳腺癌中,PEAK1与ZEB1和INHBA形成信号轴,促进肿瘤进展和拉帕替尼耐药性。间充质干细胞和癌相关成纤维细胞表达高水平PEAK1蛋白,以PEAK1依赖性方式促进HER2阳性乳腺癌细胞的肿瘤发生、拉帕替尼耐药性和转移[9]。

在血管生成中,PEAK1通过调节GATA2依赖性VEGFR2转录来介导血管生成。PEAK1基因缺失导致严重的新血管形成缺陷,这是由于EC增殖、存活和迁移不足。PEAK1通过结合并增加转录因子GATA结合蛋白2(GATA2)的蛋白稳定性来调节VEGFR2表达[8]。

综上所述,PEAK1在多种肿瘤中发挥重要作用,包括乳腺癌、结直肠癌、甲状腺癌、前列腺癌和黑色素瘤。PEAK1在肿瘤进展、转移和化疗耐药性中发挥重要作用。此外,PEAK1还在血管生成和细胞分化和信号传导中发挥作用。因此,PEAK1可能是肿瘤治疗的潜在靶点。

参考文献:
1. Wang, Xingang, Zheng, Yan, Wang, Yu. 2021. PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer. In Clinical and experimental medicine, 22, 393-402. doi:10.1007/s10238-021-00761-5. https://pubmed.ncbi.nlm.nih.gov/34554318/
2. Skingen, Vilde Eide, Hompland, Tord, Fjeldbo, Christina Sæten, Seierstad, Therese, Lyng, Heidi. 2023. Prostate cancer radiogenomics reveals proliferative gene expression programs associated with distinct MRI-based hypoxia levels. In Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 188, 109875. doi:10.1016/j.radonc.2023.109875. https://pubmed.ncbi.nlm.nih.gov/37640161/
3. Agajanian, Megan, Campeau, Anaamika, Hoover, Malachia, Klemke, Richard L, Kelber, Jonathan A. 2015. PEAK1 Acts as a Molecular Switch to Regulate Context-Dependent TGFβ Responses in Breast Cancer. In PloS one, 10, e0135748. doi:10.1371/journal.pone.0135748. https://pubmed.ncbi.nlm.nih.gov/26267863/
4. Pan, Min, Yin, Xiaohui, Huang, Yi-Chuan. . Pseudopodium enriched atypical kinase 1(PEAK1) promotes invasion and of melanoma cells by activating JAK/STAT3 signals. In Bioengineered, 12, 5045-5055. doi:10.1080/21655979.2021.1961661. https://pubmed.ncbi.nlm.nih.gov/34365903/
5. Ding, Chenbo, Tang, Wendong, Wu, Hailu, Wen, Kunming, Wu, Guoqiu. 2018. The PEAK1-PPP1R12B axis inhibits tumor growth and metastasis by regulating Grb2/PI3K/Akt signalling in colorectal cancer. In Cancer letters, 442, 383-395. doi:10.1016/j.canlet.2018.11.014. https://pubmed.ncbi.nlm.nih.gov/30472186/
6. Wang, Qiuhan, Hao, Fengyun, Ning, Liang, Sun, Chong. 2024. Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring BRAFV600E to Vemurafenib by Bim upregulation. In Histology and histopathology, 39, 1159-1165. doi:10.14670/HH-18-705. https://pubmed.ncbi.nlm.nih.gov/38284248/
7. Huang, Lanlan, Wen, Chuangyu, Yang, Xiangling, Wang, Jianping, Liu, Huanliang. 2018. PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d. In Cell death & disease, 9, 271. doi:10.1038/s41419-018-0320-8. https://pubmed.ncbi.nlm.nih.gov/29449544/
8. Wang, Huawei, Lapek, John, Fujimura, Ken, Cheresh, David A, Klemke, Richard L. 2018. Pseudopodium-enriched atypical kinase 1 mediates angiogenesis by modulating GATA2-dependent VEGFR2 transcription. In Cell discovery, 4, 26. doi:10.1038/s41421-018-0024-3. https://pubmed.ncbi.nlm.nih.gov/29872538/
9. Hamalian, Sarkis, Güth, Robert, Runa, Farhana, Zervantonakis, Ioannis K, Kelber, Jonathan A. 2021. A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers. In Oncogene, 40, 5224-5235. doi:10.1038/s41388-021-01906-2. https://pubmed.ncbi.nlm.nih.gov/34239043/