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PTK6/GAB1 信号的干扰抑制了宫颈癌细胞的增殖、侵袭和迁移。

Interference of PTK6/GAB1 signaling inhibits cell proliferation, invasion, and migration of cervical cancer cells.

机构信息

Department of Gynecology, Southern University of Science and Technology Hospital, Shenzhen, Guangdong 518055, P.R. China.

出版信息

Mol Med Rep. 2022 Sep;26(3). doi: 10.3892/mmr.2022.12800. Epub 2022 Jul 27.

Abstract

Protein tyrosine kinase 6 (PTK6) has shown important cancer‑promoting effects in a variety of cancer types. Nonetheless, its vital role in cervical cancer has not been completely elucidated. The present study sought to address whether PTK6 is involved in the malignant progression of cervical cancer via its interaction with GRB2‑associated binding 1 (GAB1). Western blotting was used to examine PTK6 and GAB1 expression levels. Cell Counting Kit‑8, Transwell, wound healing, and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assays were performed to estimate the corresponding proliferative, migratory, invasive, and apoptotic abilities of the cells. Co‑immunoprecipitation (Co‑IP) assays confirmed binding of PTK6 to GAB1. The results revealed that the expression levels of PTK6 and GAB1 were markedly increased in cervical cancer cell lines compared with those noted in normal cervical epithelial cells. The cell proliferative, invasive, and migratory activities of cervical cancer cells were reduced in the absence of PTK6 expression, whereas the induction of apoptosis was aggravated under these conditions. The results of the Co‑IP assay indicated that PTK6 expression was positively associated with GAB1. In addition, the suppressive effect of PTK6 silencing on the malignant phenotypes of cervical cancer cells was reversed following overexpression of GAB1. In summary, the present study indicated that knockdown of PTK6 expression protected against the malignant progression of cervical cancer, while overexpression of GAB1 counteracted the inhibitory effects of PTK6 knockdown on cervical cancer cells.

摘要

蛋白酪氨酸激酶 6(PTK6)在多种癌症类型中表现出重要的致癌作用。然而,其在宫颈癌中的重要作用尚未完全阐明。本研究旨在探讨 PTK6 是否通过与衔接蛋白 GRB2 相关结合蛋白 1(GAB1)相互作用参与宫颈癌的恶性进展。采用 Western blot 检测 PTK6 和 GAB1 的表达水平。通过细胞计数试剂盒-8 检测、Transwell 检测、划痕愈合检测和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记检测,评估细胞相应的增殖、迁移、侵袭和凋亡能力。采用免疫共沉淀(Co-IP)检测证实 PTK6 与 GAB1 结合。结果显示,与正常宫颈上皮细胞相比,宫颈癌细胞系中 PTK6 和 GAB1 的表达水平明显升高。在没有 PTK6 表达的情况下,宫颈癌细胞的增殖、侵袭和迁移活性降低,而在这些条件下,细胞凋亡的诱导加剧。Co-IP 检测结果表明,PTK6 的表达与 GAB1 呈正相关。此外,过表达 GAB1 逆转了 PTK6 沉默对宫颈癌细胞恶性表型的抑制作用。综上所述,本研究表明,下调 PTK6 表达可防止宫颈癌的恶性进展,而过表达 GAB1 则抵消了 PTK6 沉默对宫颈癌细胞的抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9330/9366152/7e5b07f87b9a/mmr-26-03-12800-g00.jpg

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