MAPK and AKT Pathway Intersection in Neuroblastoma Cells

Abstract

One of the most important contributing factors for cancer development is the aberrant activation of mitogenic MAPK and AKT survival pathways. Abnormal activities of these pathways also indicates poor prognosis as a result of drug resistance in cancer treatment. It is revealed that there is a cross-talk between these two signaling cascades and they act together by one triggering the other performing an anti-apoptotic effect. It is evident that interplay between MAPK and AKT pathways is at the center of poor prognosis especially in neuroblastoma. However, it is still unknown what is there at the heart of this interaction. In this mini review, tumorigenic and chemotherapy-resistant effects of MAPK and AKT pathways and also the effect of their cross-talk in neuroblastoma and other cancers is summarized, Then, several cross-talk nodes between two pathways, which is used by the cells in a context-dependent mode is briefly explained. Finally, summarizing the studies giving insights about certain cell cycle regulators which may be involved in the intersection of these signaling pathways, importance of analyzing not only direct crosstalk between the members of these two pathways, but also mediator-dependent interactions are emphasized, since it is crucial to understand these interactions to choose the appropriate molecular targets for both diagnosis and treatment especially of neuroblastoma which has a very poor prognosis.

Salicylidene acylhydrazides attenuate survival of SH-SY5Y neuroblastoma cells through affecting mitotic regulator Speedy/RINGO and ERK/MAPK–PI3K/AKT signaling

“…However, the role of these interactions in cancer, especially in neuroblastoma is not yet known. At this point, data are available that strengthen the probability that one of the contributors of these interactions on PI3K/AKT and ERK/MAPK signaling pathways is the Speedy/RINGO protein, which is an unconventional cell cycle regulator and plays a pivotal role in cancer [12,13]. Speedy/RINGO, which is a cell cycle regulatory protein that is different from classical cell cycle regulators in its mechanism of action and has been shown in Xenopus oocytes for the first time, controls CDK2 activity and G 1 -S phase transition in the progression of the cell cycle [14].…”