Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.
Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.
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Caspase-3调控结肠癌细胞的迁移、侵袭和转移
DOI：
10.1002/ijc.31374
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发表时间：
2018-08-15
影响因子：
6.4
通讯作者：
Li CY
中科院分区：
文献类型：
--
作者：
Zhou M;Liu X;Li Z;Huang Q;Li F;Li CY
Caspase-3 (CASP3) 是细胞凋亡的主要介质，在细胞暴露于细胞毒性药物、放射治疗或免疫治疗期间被激活。它经常被用作癌症治疗功效的标志。然而，最近的报道表明，caspase-3还具有非凋亡作用，例如促进肿瘤复发和肿瘤血管生成。因此，caspase-3在肿瘤进展中的作用仍有待明确。在本研究中，我们利用CRISPR技术建立了caspase-3敲除（KO）结肠癌细胞系。在体外，软琼脂实验中，Caspase-3 敲除的 HCT116 细胞的克隆形成能力显着降低。与对照细胞相比，它们的侵袭性也明显更小，对辐射和丝裂霉素 C 更敏感。在体内，CASP3KO 细胞形成肿瘤的速度与对照细胞相似，但对放射治疗明显更敏感。当皮下或静脉注射时，它们也不太容易发生肺部转移。在机制水平上，与亲本 HCT116 细胞相比，caspase-3 基因敲除似乎导致 EMT 表型减少。事实上，与对照细胞相比，它们的 E-钙粘蛋白表达显着增加，N-钙粘蛋白、Snail、Slug 和 ZEB1 表达显着减少。因此，针对caspase-3的治疗不仅可以增加癌细胞对化疗和放疗的敏感性，还可以抑制癌细胞的侵袭和转移。
Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro,caspase-3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase-3 gene knockout appeared to cause reduced EMT phenotypes when compared with parental HCT116 cells. Indeed, they showed significantly increased E-cadherin expression, reduced N-cadherin, Snail, Slug, and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase-3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastases.
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垂死的神经胶质瘤细胞通过 caspase 3 依赖性机制建立促血管生成微环境
影响因子：
9.7
作者：
Feng X;Yu Y;He S;Cheng J;Gong Y;Zhang Z;Yang X;Xu B;Liu X;Li CY;Tian L;Huang Q
通讯作者：
Huang Q
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1073/pnas.77.2.1039
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CIFONE, MA;FIDLER, IJ
通讯作者：
FIDLER, IJ
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5
作者：
Jonges, LE;Nagelkerke, JF;Kuppen, PJK
通讯作者：
Kuppen, PJK