Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Markey Cancer Center, Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40508, USA.
Cells. 2022 Dec 15;11(24):4057. doi: 10.3390/cells11244057.
The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known about the role of MST4 in breast cancer, and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here we report that overexpression of MST4 in breast cancer results in enhanced cell growth, migration, and invasion, whereas inhibition of MST4 expression significantly attenuates these properties. Further study shows that MST4 promotes EMT by activating Akt and its downstream signaling molecules such as E-cadherin/N-cadherin, Snail, and Slug. MST4 also activates AKT and its downstream pro-survival pathway. Furthermore, by analyzing breast cancer patient tissue microarray and silicon datasets, we found that MST4 expression is much higher in breast tumor tissue compared to normal tissue, and significantly correlates with cancer stage, lymph node metastasis and a poor overall survival rate ( 0.05). Taken together, our findings demonstrate the oncogenic potential of MST4 in breast cancer, highlighting its role in cancer cell proliferation, migration/invasion, survival, and EMT, suggesting a possibility that MST4 may serve as a novel therapeutic target for breast cancer.
哺乳动物 STE 20 样蛋白激酶 4（MST4）基因在多种癌症类型中高度表达，但关于 MST4 在乳腺癌中的作用知之甚少，MST4 在上皮-间充质转化（EMT）过程中的功能也尚未完全阐明。在这里，我们报告在乳腺癌中过表达 MST4 会导致细胞生长、迁移和侵袭能力增强，而抑制 MST4 的表达则显著减弱这些特性。进一步的研究表明，MST4 通过激活 Akt 及其下游信号分子，如 E-钙黏蛋白/N-钙黏蛋白、Snail 和 Slug，促进 EMT。MST4 还激活 AKT 及其下游的促生存途径。此外，通过分析乳腺癌患者组织微阵列和硅数据集，我们发现 MST4 在乳腺癌组织中的表达明显高于正常组织，并且与癌症分期、淋巴结转移和总体生存率低显著相关（P<0.05）。总之，我们的研究结果表明 MST4 在乳腺癌中具有致癌潜能，突出了其在癌细胞增殖、迁移/侵袭、存活和 EMT 中的作用，表明 MST4 可能成为乳腺癌的一种新的治疗靶点。
