Aberrantly high activation of a FoxM1-STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers.
Aberrantly high activation of a FoxM1-STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers.
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FoxM1-STMN1轴的异常高激活有助于FoxM1驱动的癌症的进展和肿瘤发生
DOI：
10.1038/s41392-020-00396-0
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发表时间：
2021-02-01
影响因子：
39.3
通讯作者：
Yang A
中科院分区：
文献类型：
--
作者：
Liu J;Li J;Wang K;Liu H;Sun J;Zhao X;Yu Y;Qiao Y;Wu Y;Zhang X;Zhang R;Yang A
叉头盒蛋白M1（FoxM 1）是一种转录因子，在癌症的发生和发展中起关键作用。然而，FoxM 1的一般调节机制仍然有限。STMN 1是一种微管结合蛋白，可抑制微管二聚体的组装或促进微管的解聚。据报道，它是肿瘤患者临床化疗紫杉醇耐药的主要反应因素。但STMN 1异常高表达在肿瘤细胞中的作用及其调控机制尚不清楚。在这项研究中，我们使用公共数据库和组织芯片来分析FoxM 1和STMN 1的表达模式，发现FoxM 1和STMN 1在多种类型的癌症中存在强正相关性。建立慢病毒介导的FoxM 1/STMN 1基因敲减细胞系，通过体外细胞活力测定、平板克隆形成测定、软琼脂试验和体内异种移植小鼠模型研究FoxM 1/STMN 1基因的功能。我们的研究结果表明，FoxM 1通过上调STMN 1促进细胞增殖。进一步的ChIP分析表明FoxM 1在转录水平上调STMN 1。预后分析显示，FoxM 1和STMN 1的高水平与实体瘤的不良预后有关。此外，FoxM 1和STMN 1的高共表达与不良预后具有更显著的相关性。我们的研究结果表明，一般FoxM 1-STMN 1轴有助于细胞增殖和肿瘤发生在肝细胞癌，胃癌和结直肠癌。FoxM 1和STMN 1的组合可以成为预后预测的更精确的生物标志物。
Fork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.
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影响因子：
3.8
作者：
Ahmad, Aamir;Wang, Zhiwei;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
4
作者：
Shrestha, Deepmala;Kim, Namil;Song, Kiwon
通讯作者：
Song, Kiwon
DOI：
10.1158/1541-7786.mcr-16-0372
发表时间：
2017-07
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Vetter NS;Kolb EA;Mills CC;Sampson VB
通讯作者：
Sampson VB
影响因子：
11.2
作者：
Gartel AL
通讯作者：
Gartel AL
影响因子：
50.3
作者：
Aytes A;Mitrofanova A;Lefebvre C;Alvarez MJ;Castillo-Martin M;Zheng T;Eastham JA;Gopalan A;Pienta KJ;Shen MM;Califano A;Abate-Shen C
通讯作者：
Abate-Shen C