TRIP suppresses cell proliferation and invasion in choroidal melanoma via promoting the proteasomal degradation of Twist1
FEBS LETTERS
Authors: Wei, Chao; Zhao, Xiaofei; Wang, Lei; Zhang, Han
Abstract
Choroidal melanoma (CM) remains the most prevalent form of intraocular malignancy, and the prognosis of affected patients is poor. While the E3 ubiquitin ligase TRAF-interacting protein (TRIP) is known to play key regulatory roles in multiple diseases, its relevance in CM remains uncertain. In the present study, we found that TRIP overexpression is sufficient to inhibit the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of CM cellsin vitro, whereas the opposite phenotypes are observed following TRIP knockdown. We further determined that TRIP is able to promote the K48-polyubiquitination of EMT-associated transcription factor Twist-related protein 1, thereby suppressing EMT progression. Together, our results suggest that TRIP plays an important role in regulating the progression of CM and that it may therefore be an important therapeutic target for the treatment of this disease.
To be more precise: the role of intracellular trafficking in development and pattern formation
BIOCHEMICAL SOCIETY TRANSACTIONS
Authors: York, Harrison M.; Coyle, Joanne; Arumugam, Senthil
Abstract
Living cells interpret a variety of signals in different contexts to elucidate functional responses. While the understanding of signalling molecules, their respective receptors and response at the gene transcription level have been relatively well-explored, how exactly does a single cell interpret a plethora of time-varying signals? Furthermore, how their subsequent responses at the single cell level manifest in the larger context of a developing tissue is unknown. At the same time, the biophysics and chemistry of how receptors are trafficked through the complex dynamic transport network between the plasma membrane-endosome-lysosome-Golgi-endoplasmic reticulum are much more well-studied. How the intracellular organisation of the cell and inter-organellar contacts aid in orchestrating trafficking, as well as signal interpretation and modulation by the cells are beginning to be uncovered. In this review, we highlight the significant developments that have strived to integrate endosomal trafficking, signal interpretation in the context of developmental biology and relevant open questions with a few chosen examples. Furthermore, we will discuss the imaging technologies that have been developed in the recent past that have the potential to tremendously accelerate knowledge gain in this direction while shedding light on some of the many challenges.