4.6 Article

Cancer-derived IgG involved in cisplatin resistance through PTP-BAS/Src/PDK1/AKT signaling pathway

Journal

ORAL DISEASES
Volume 27, Issue 3, Pages 464-474

Publisher

WILEY
DOI: 10.1111/odi.13583

Keywords

cancer-derived IgG; cisplatin resistance; head and neck squamous cell carcinoma; PTP-BAS; Src

Funding

  1. National Natural Science Foundation of China [81472764]

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The study showed that knockdown of cancer-derived IgG (CIgG) enhanced the effects of cisplatin in oral squamous cell carcinoma through the PTP-BAS/Src/PDK1/AKT signaling pathway. The knockdown of CIgG promoted cisplatin-induced cell apoptosis and inhibition of cell proliferation, migration, and invasion. The study also found that cisplatin upregulated CIgG expression and phosphorylation of AKT and PDK1.
Objectives This study aimed to explore whether knockdown of cancer-derived IgG (CIgG) could enhance cisplatin-induced anti-cancer effects. Materials and methods Cancer-derived IgG was knocked down by siRNA or Tet-on shRNA in the absence or presence of cisplatin in WSU-HN6 or CAL27 cells. Cell proliferation, apoptosis, and mobility were evaluated using CCK-8, flow cytometry, and transwell assays, respectively. Molecular events were investigated using real-time PCR and Western blot assays. Results Knockdown of CIgG significantly promoted cisplatin-induced apoptosis and inhibition of cell proliferation, migration, and invasion. Cisplatin upregulated CIgG expression and phosphorylation of AKT and PDK1, while knockdown of CIgG downregulated phosphorylation of AKT and PDK1, and blocked cisplatin-induced upregulation of AKT and PDK1 phosphorylation. Moreover, knockdown of CIgG blocked cisplatin-induced upregulation of Src phosphorylation, and knockdown of Src blocked cisplatin-induced upregulation of AKT and PDK1 phosphorylation. Overexpression of Src upregulated AKT and PDK1 phosphorylation. Furthermore, knockdown of CIgG upregulated PTP-BAS mRNA and protein expression, whereas cisplatin downregulated PTP-BAS protein, but not mRNA expression; knockdown of PTP-BAS upregulated phosphorylation of Src, PDK1, AKT, and blocked CIgG knockdown-mediated enhancement of cisplatin-induced inhibition of cell proliferation. Conclusion Knockdown of CIgG enhanced the anti-cancer effects of cisplatin through PTP-BAS/Src/PDK1/AKT signaling pathway in oral squamous cell carcinoma.

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