PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells

• Published in: Future science OA 2020-06, Vol.6 (5), p.FSO463-FSO463
• Main Authors: Dietel, Eric, Brobeil, Alexander, Tag, Claudia, Gattenloehner, Stefan, Wimmer, Monika
• Format: Article
• Language: English
• Subjects: breast cancer; Her2; IKK-16; NFκB; PDTC; protein–protein interactions; PTPIP51
• ISSN: 2056-5623; 2056-5623
• DOI: 10.2144/fsoa-2019-0136

PTPIP51 interacts with NFκB signaling at the RelA and IκB level. NFκB signaling is linked to the initiation, progression and metastasis of breast cancer. Her2-amplified breast cancer cells frequently display activation of the NFκB signaling. We aimed to clarify the effects of NFκB inhibition on the NFκB- and MAPK-related interactome of PTPIP51 and cell viability in HaCat cells and SKBR3 cells. 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. IKK-16 selectively inhibits cell viability of SKBR3 cells. In addition, PTPIP51 might serve as the mediator between NFκB signaling and the MAPK pathway in SKBR3. 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. NFκB signaling represents a downstream signaling pathway that can be activated by Her2. In this study, we demonstrated that inhibition of NFκB 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 NFκB signaling. This signaling pathway could therefore be a target for future drug development.