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蛋白酪氨酸磷酸酶 1B(PTP1B)通过激活Src 促进黑色素瘤细胞的进展。

Protein tyrosine phosphatase 1B(PTP1B) promotes melanoma cells progression through Src activation.

机构信息

Department of Plastic Surgery, Zhongshan Hospital, Fudan University Shanghai, China.

Department of Plastic Surgery, the First Affiliated Hospital of Ustc, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China.

出版信息

Bioengineered. 2021 Dec;12(1):8396-8406. doi: 10.1080/21655979.2021.1988376.

Abstract

Previous studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B) can promote tumor progression in breast cancer, colon cancer and prostate cancer. Additionally, PTP1B also acts as a tumor suppressor in esophageal cancer and lymphoma. These findings suggest that PTP1B functions as a double-faceted molecule in tumors. However, the role of PTP1B in malignant melanoma (MM) is still unknown. PTP1B expression in normal and melanoma tissues was evaluated by GEO analysis and immunohistochemistry. The effects of PTP1B on cell migration and invasion were evaluated in melanoma cells with up - and downregulated PTP1B expression. In this study, we initially demonstrated that the expression of PTP1B in malignant melanoma tissue is significantly higher than its expression in benign nevus tissue and indicated poor survival of malignant melanoma patients. In vitro studies have demonstrated that inhibition of PTP1B suppresses and overexpression of PTP1B promotes migration and invasion of melanoma cells. Moreover, we found that PTP1B could interact with Src via coimmunoprecipitation and dephosphorylation of the Src at Tyr530 site. Collectively, our study revealed that PTP1B can promote melanoma cell metastasis by interacting with Src and provides a theoretical basis for future applications of PTP1B inhibitors in the treatment of malignant melanoma.

摘要

先前的研究表明,蛋白酪氨酸磷酸酶 1B(PTP1B)可以促进乳腺癌、结肠癌和前列腺癌的肿瘤进展。此外,PTP1B 还在食管癌和淋巴瘤中作为肿瘤抑制因子发挥作用。这些发现表明 PTP1B 在肿瘤中具有双重作用。然而,PTP1B 在恶性黑色素瘤(MM)中的作用仍不清楚。通过 GEO 分析和免疫组织化学评估 PTP1B 在正常和黑色素瘤组织中的表达。通过上调和下调 PTP1B 表达,评估 PTP1B 对黑色素瘤细胞迁移和侵袭的影响。在这项研究中,我们最初证明 PTP1B 在恶性黑色素瘤组织中的表达明显高于良性痣组织中的表达,并提示恶性黑色素瘤患者的生存不良。体外研究表明,抑制 PTP1B 可抑制,过表达 PTP1B 可促进黑色素瘤细胞的迁移和侵袭。此外,我们发现 PTP1B 可以通过共免疫沉淀与 Src 相互作用,并使 Src 的 Tyr530 位点去磷酸化。综上所述,我们的研究揭示了 PTP1B 通过与 Src 相互作用促进黑色素瘤细胞转移,并为未来应用 PTP1B 抑制剂治疗恶性黑色素瘤提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b20/8806946/2c312167c820/KBIE_A_1988376_F0001_OC.jpg

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