Prostate cancers often exhibit alterations in genes that are involved in differentiation, and they also co-express some basal and luminal markers, pointing to defects in differentiation contributing to tumorigenesis. In their study on page 1952, Cindy Miranti and colleagues sought to understand how the p38-MAPK, MYC and Notch signalling pathways, known to be involved in differentiation, work together in normal prostate differentiation. By utilising an in vitro differentiation model of human basal prostate epithelial cells, they first asked whether the p38-MAPK family is involved in the regulation of Notch3, whose induction coincides with the appearance of suprabasal cells during prostate differentiation. Indeed, inhibition or knockdown of p38-MAPK prevented differentiation, whereas constitutive activation of p38-MAPK increased the levels of Notch3 in a MYC-dependent manner. This suggests that Notch3 is a MYC target that is downstream of p38-MAPK, whereas it had been thought to act upstream of MYC. With regard to the underlying mechanisms, the authors show that Notch3 is regulated both transcriptionally, including via MYC, and post-transcriptionally, through a p38-MAPK-mediated increase in its mRNA stability. Taken together, this work thus provides new insights into the crosstalk between p38-MAPK, MYC and Notch signalling during differentiation that could be exploited for targeting tumours that arise from dysregulated differentiation programmes.
Crosstalk between p38-MAPK, MYC and Notch signalling in differentiation Free
Crosstalk between p38-MAPK, MYC and Notch signalling in differentiation. J Cell Sci 1 June 2017; 130 (11): e1104. doi:
Download citation file:
Advertisement
Cited by
JCS fast-track option

Have a paper that has been reviewed elsewhere? JCS is pleased to consider such manuscripts for fast-tracked decision making. Send us your manuscript together with the full set of reviews and decision letters, and we will make an initial decision within one week.
Special Issue – Cell Biology of Mitochondria

Our special issue on ‘Cell Biology of Mitochondria’ is now complete. Explore this issue and read the Editorial from our Guest Editors Ana J. García-Sáez and Heidi McBride.
Save the date – Imaging Cell Dynamics

We are delighted to announce that we will be hosting a 2026 Imaging Cell Dynamics meeting. This meeting will provide a unique opportunity to bring together experts working at the interface between cell biology and imaging. Save the date for 11-14 May 2026 and register for more information.
Origin and evolution of mitochondrial inner membrane composition

In this Review, Kailash Venkatraman and colleagues provide an examination of the morphological similarities between prokaryotic intracytoplasmic membranes and mitochondrial inner membranes, and whether cristae evolution has driven specialisation of the mitochondrial lipidome.
Resolution in super-resolution microscopy
Super-resolution microscopy (SRM) has emerged as a powerful tool for biological discovery. In this Perspective, Kirti Prakash and colleagues compile expert opinions on crucial, yet often overlooked, aspects of SRM that are essential for maximising its benefits and advancing the field.