PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells and provides a bypass mechanism for NFκB inhibition

Abstract Background Previous studies of our group revealed an association of the scaffolding protein Protein Tyrosine Phosphatase Interacting Protein 51 (PTPIP51) with the NFκB signaling on the RelA and IκB level. The NFκB signaling plays a pivotal role in many different tumor entities. Especially HER2 amplified breast cancer cells frequently display activation of the NFκB signaling. Here, the NFκB signaling is linked to the initiation, progression, and the metastasis of the breast cancer. Furthermore, a large body of evidence associates the NFκB signaling with the development of therapy resistance. We aimed to clarify the effects of NFκB inhibition on the NFκB- and the MAPK-related interactome of PTPIP51 in HaCat cells and SKBR3 cells and their correlation with cell viability. Results Both NFκB signaling inhibitors, PDTC and IKK-16, reduced the cell viability of SKBR3 cells. IKK-16 selectively reduced the cell viability in SKBR3 cells at 5µM, while the viability of HaCat cells was not affected. PDTC impaired the cell viability of both cell lines and induced a formation of the Raf1/14-3-3/PTPIP51 complex in SKBR3 cells, indicating a shift of PTPIP51 into MAPK signaling. The MAPK-related interactome of PTPIP51 remained unaffected by IKK-16. Conclusion (1)The effectiveness and selectivity of NFκB inhibition in malignant and non-malignant signaling systems depends on the level of the targeted signaling molecule. (2) PTPIP51 might serve as the mediator between the NFκB signaling and the MAPK pathway in SKBR3 cells upon NFκB inhibition.