PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells
PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells
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DOI：
10.2144/fsoa-2019-0136
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发表时间：
2020-06-01
影响因子：
2.5
通讯作者：
Wimmer, Monika
中科院分区：
文献类型：
--
作者：
Dietel, Eric;Brobeil, Alexander;Wimmer, Monika
目的：PTPIP51在RelA和I κ B水平上与NF κ B信号相互作用。NF κ B信号与乳腺癌的发生、发展和转移有关。her2扩增的乳腺癌细胞经常表现出NF κ B信号的激活。我们旨在阐明抑制NF κ B对HaCat细胞和SKBR3细胞中PTPIP51与NF κ B和mapk相关的相互作用以及细胞活力的影响。结果：IKK-16选择性降低SKBR3细胞的细胞活力。PDTC在SKBR3细胞中诱导了Raf1/14-3-3/PTPIP51复合物的形成，表明PTPIP51向MAPK信号转导。结论：IKK-16选择性抑制SKBR3细胞活力。此外，PTPIP51可能是SKBR3中NF κ B信号通路和MAPK通路之间的中介。摘要乳腺癌是妇女中最常见的恶性肿瘤。乳腺癌的预后和治疗取决于激素和表面受体（如Her2）的表达，它们通过激活下游信号通路促进肿瘤的生长和侵袭。NF κ B信号通路是一条可被Her2激活的下游信号通路。在这项研究中，我们证明了IKK-16抑制NF κ B信号传导会降低Her2扩增的乳腺癌细胞的细胞活力。此外，我们发现PTPIP51是MAPK通路和NF κ B信号传导之间串扰的潜在中介。因此，这种信号通路可能成为未来药物开发的目标。
Aim: PTPIP51 interacts with NF kappa B signaling at the RelA and I kappa B level. NF kappa B signaling is linked to the initiation, progression and metastasis of breast cancer. Her2-amplified breast cancer cells frequently display activation of the NF kappa B signaling. We aimed to clarify the effects of NF kappa B inhibition on the NF kappa B- and MAPK-related interactome of PTPIP51 and cell viability in HaCat cells and SKBR3 cells. Results: IKK-16 selectively reduced cell viability in SKBR3 cells. PDTC induced a formation of the Raf1/14-3-3/PTPIP51 complex in SKBR3 cells, indicating a shift of PTPIP51 into MAPK signaling. Conclusion: IKK-16 selectively inhibits cell viability of SKBR3 cells. In addition, PTPIP51 might serve as the mediator between NF kappa B signaling and the MAPK pathway in SKBR3.Lay abstract Breast cancer is the most common cancerous disease among women. Prognosis and therapy of breast cancer depends on the expression of hormone and surface receptors such as Her2, which promote tumor growth and invasion via activation of downstream signaling pathways. NF kappa B signaling represents a downstream signaling pathway that can be activated by Her2. In this study, we demonstrated that inhibition of NF kappa B signaling with IKK-16 reduces cell viability in breast cancer cells with amplified Her2. Furthermore, we identified PTPIP51 as a potential mediator of crosstalks between the MAPK pathway and NF kappa B signaling. This signaling pathway could therefore be a target for future drug development.