Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2 Expression.
Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2 Expression.
复制标题
拉帕替尼通过影响 PKM2 表达抑制乳腺癌细胞增殖
DOI：
10.1177/1533034617749418
复制
发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Guan M;Tong Y;Guan M;Liu X;Wang M;Niu R;Zhang F;Dong D;Shao J;Zhou Y
丙酮酸激酶M2在多种肿瘤细胞中表达，在有氧糖酵解中起关键作用，也具有非糖酵解功能，可以调节转录和细胞增殖。本研究的结果表明，表皮生长因子受体激活诱导丙酮酸激酶型M2核转位。为了进一步确定丙酮酸激酶M2型和表皮生长因子受体之间的关系，我们分析了乳腺的病理数据，并进行了表皮生长因子受体/人表皮生长因子受体2敲除，以揭示丙酮酸激酶M2型与表皮生长因子受体和人表皮生长因子受体2相关。拉帕替尼是一种小分子表皮生长因子受体酪氨酸激酶抑制剂，可抑制表皮生长因子受体和人表皮生长因子受体2，但其对丙酮酸激酶M2型的作用仍不清楚。因此，我们进行了Western印迹和逆转录聚合酶链反应，并分析了乳腺的病理数据，结果表明拉帕替尼抑制丙酮酸激酶M2型表达。我们进一步发现，抗肿瘤药物拉帕替尼通过影响丙酮酸激酶M2型表达来抑制乳腺癌细胞增殖，这是基于细胞计数试剂盒-8分析和丙酮酸激酶M2型过表达实验。信号转导子和转录激活子3是一种与细胞增殖相关的转录因子，也是唯一一种与丙酮酸激酶M2型相互作用的转录因子，我们在人乳腺癌细胞MDA-MB-231和人乳腺癌细胞SK-BR-231中进行了丙酮酸激酶M2型敲低实验。3细胞系，并检查对信号转导子和转录激活子3以及磷酸化信号转导子和转录激活子3水平的影响。结果表明，丙酮酸激酶M2型调节信号转导和转录激活因子3和磷酸化Stat 3（Tyr 705）的表达。与之前的报告一起，我们的研究结果表明拉帕替尼通过影响丙酮酸激酶M2型表达来抑制乳腺癌细胞增殖，这导致信号转导和转录激活因子3以及磷酸化信号转导和转录激活因子3的减少。
Pyruvate kinase type M2, which is expressed in multiple tumor cell types and plays a key role in aerobic glycolysis, also has nonglycolytic functions and can regulate transcription and cell proliferation. The results of this study show that epidermal growth factor receptor activation induces pyruvate kinase type M2 nuclear translocation. To further determine the relationship between pyruvate kinase type M2 and epidermal growth factor receptor, we analyzed pathological data from mammary glands and performed epidermal growth factor receptor/human epidermal growth factor receptor 2 knockdown to reveal that pyruvate kinase type M2 is associated with epidermal growth factor receptor and human epidermal growth factor receptor 2. Lapatinib is a small molecule epidermal growth factor receptor tyrosine kinase inhibitor that can inhibit epidermal growth factor receptor and human epidermal growth factor receptor 2, though its effect on pyruvate kinase type M2 remains elusive. Accordingly, we performed Western blotting and reverse transcription polymerase chain reaction and analyzed pathological data from mammary glands, with results suggesting that lapatinib inhibits pyruvate kinase type M2 expression. We further found that the antitumor drug lapatinib inhibits breast cancer cell proliferation by influencing pyruvate kinase type M2 expression, as based on Cell Counting Kit-8 analyses and pyruvate kinase type M2 overexpression experiments. Signal transducer and activator of transcription 3, which is a transcription factor-associated cell proliferation and the only transcription factor that interacts with pyruvate kinase type M2, we performed pyruvate kinase type M2 knockdown experiments in Human breast cancer cells MDA-MB-231 and Human breast cancer cells SK-BR-3 cell lines and examined the effect on levels of Signal transducer and activator of transcription 3 and phosphorylated Signal transducer and activator of transcription 3. The results indicate that pyruvate kinase type M2 regulates Signal transducer and activator of transcription 3 and phospho-Stat3 (Tyr705) expression. Together with previous reports, our findings show that lapatinib inhibits breast cancer cell proliferation by influencing pyruvate kinase type M2 expression, which results in a reduction in both Signal transducer and activator of transcription 3 and phosphorylated Signal transducer and activator of transcription 3.
登录
查看更多内容
DOI：
10.1186/bcr327
发表时间：
2001
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Olayioye MA
通讯作者：
Olayioye MA
影响因子：
4
作者：
Huang, Wei;Dong, Zizheng;Wang, Fang;Peng, Hui;Liu, Jing-Yuan;Zhang, Jian-Ting
通讯作者：
Zhang, Jian-Ting
DOI：
10.1016/j.biocel.2007.11.009
发表时间：
2008-01-01
影响因子：
4
作者：
Lee, Jungwoon;Kim, Hye Kyoung;Kim, Jungho
通讯作者：
Kim, Jungho
影响因子：
5.7
作者：
Nahta, Rita;Yuan, Linda X. H.;Esteva, Francisco J.
通讯作者：
Esteva, Francisco J.
影响因子：
4.6
作者：
Kozlova, Nina;Samoylenko, Anatoly;Kietzmann, Thomas
通讯作者：
Kietzmann, Thomas