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PTBP1 通过 PTEN/Akt 通路和自噬促进乳腺癌细胞的生长。

PTBP1 promotes the growth of breast cancer cells through the PTEN/Akt pathway and autophagy.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning, China.

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.

出版信息

J Cell Physiol. 2018 Nov;233(11):8930-8939. doi: 10.1002/jcp.26823. Epub 2018 Jun 1.

Abstract

Invasion and migration is the hallmark of malignant tumors as well as the major cause for breast cancer death. The polypyrimidine tract binding, PTB, protein serves as an important model for understanding how RNA binding proteins affect proliferation and invasion and how changes in the expression of these proteins can control complex programs of tumorigenesis. We have investigated some roles of polypyrimidine tract binding protein 1 (PTBP1) in human breast cancer. We found that PTBP1 was upregulated in breast cancer tissues compared with normal tissues and the same result was confirmed in breast cancer cell lines. Knockdown of PTBP1 substantially inhibited tumor cell growth, migration, and invasion. These results suggest that PTBP1 is associated with breast tumorigenesis and appears to be required for tumor cell growth and maintenance of metastasis. We further analyzed the relationship between PTBP1 and clinicopathological parameters and found that PTBP1 was correlated with her-2 expression, lymph node metastasis, and pathological stage. This will be a novel target for her-2( ) breast cancer. PTBP1 exerts these effects, in part, by regulating the phosphatase and tensin homolog-phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PTEN-PI3K/Akt) pathway and autophagy, and consequently alters cell growth and contributes to the invasion and metastasis.

摘要

浸润和转移是恶性肿瘤的特征,也是导致乳腺癌死亡的主要原因。多嘧啶 tract 结合蛋白(PTB)蛋白是理解 RNA 结合蛋白如何影响增殖和侵袭以及这些蛋白表达的变化如何控制肿瘤发生的复杂程序的重要模型。我们研究了多嘧啶 tract 结合蛋白 1(PTBP1)在人乳腺癌中的一些作用。我们发现,与正常组织相比,乳腺癌组织中 PTBP1 上调,在乳腺癌细胞系中也得到了同样的结果。PTBP1 的敲低显著抑制肿瘤细胞的生长、迁移和侵袭。这些结果表明,PTBP1 与乳腺癌的发生有关,似乎是肿瘤细胞生长和维持转移所必需的。我们进一步分析了 PTBP1 与临床病理参数之间的关系,发现 PTBP1 与 her-2 表达、淋巴结转移和病理分期相关。这将是 her-2(+)乳腺癌的一个新靶点。PTBP1 通过调节磷酸酶和张力蛋白同源物-磷酸肌醇-3-激酶/蛋白激酶 B(PTEN-PI3K/Akt)通路和自噬来发挥这些作用,从而改变细胞生长,并促进侵袭和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a2/6175200/4d33ddb809b7/JCP-233-8930-g001.jpg

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