Trends in Cell Biology最新文献

Scientific research is an exploration of the unknown. The process is full of uncertainty, missteps, delightful surprises, painful lessons, and ultimately a measure of insight into nature. In this Science and Society article I suggest a few practical strategies that helped me navigate these challenges at the earliest stages of becoming a cell biologist.

Receptor tyrosine kinase (RTK)-mediated signal transduction is fundamental to cell function and drives important cellular outcomes which, when dysregulated, can lead to malignant tumour growth and metastasis. The initiation of signals from plasma membrane-bound RTKs is subjected to multiple regulatory mechanisms that control downstream effector protein recruitment and function. The high propensity of RTKs to condense via liquid-liquid phase separation (LLPS) into membraneless organelles with downstream effector proteins provides a further fundamental mechanism for signal regulation. Herein we highlight how this phenomenon contributes to cancer signalling and consider the potential impact of LLPS on outcomes for cancer patients.

Lipids are essential molecules that play key roles in cell physiology by serving as structural components, for storage of energy, and in signal transduction. Hence, efficient regulation and maintenance of lipid homeostasis are crucial for normal cellular and tissue function. In the past decade, increasing research has shown the importance of ubiquitination in regulating the stability of key players in different aspects of lipid metabolism. This review describes recent insights into the regulation of lipid metabolism by ubiquitin signaling, discusses how ubiquitination can be targeted in diseases characterized by lipid dysregulation, and identifies areas that require further research.

Calcium (Ca²⁺) plays a pivotal role in cellular signal transmission by triggering downstream signaling in response to an increase in the cytosolic Ca²⁺ concentration. Intracellular organelles serve as Ca²⁺ stores that induce differently shaped Ca²⁺ signals. We discuss a study by Yuan et al. that investigated the interplay between the lysosomal two-pore channel 2 (TPC2) and endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptors (IP₃Rs).

The critical redox cofactor NAD⁺ was recently reported to serve as an RNA cap in both eukaryotes and prokaryotes. However, its reversible regulation and biological functions remain unclear. Here, we provide insights into its discovery, capping and decapping mechanisms, for further discovery of their potential functional implications.

H3.3 is a highly conserved nonreplicative histone variant. H3.3 is enriched in promoters and enhancers of active genes, but it is also found within suppressed heterochromatin, mostly around telomeres. Accordingly, H3.3 is associated with seemingly contradicting functions: It is involved in development, differentiation, reprogramming, and cell fate, as well as in heterochromatin formation and maintenance, and the silencing of developmental genes. The emerging view is that different cellular contexts and histone modifications can promote opposing functions for H3.3. Here, we aim to provide an update with a focus on H3.3 functions in early mammalian development, considering the context of embryonic stem cell maintenance and differentiation, to finally conclude with emerging roles in cancer development and cell fate transition and maintenance.

Breast cancer (BC) involves complex signaling networks characterized by extensive cross-communication and feedback loops between and within multiple signaling cascades. Many of these signaling pathways are driven by genetic alterations of oncogene and/or tumor-suppressor genes and are influenced by various environmental cues. We describe unique roles of the non-receptor tyrosine kinase (NRTK) PYK2 in signaling integration and feedback looping in BC. PYK2 functions as a signaling hub in various cascades, and its involvement in positive and negative feedback loops enhances signaling robustness, modulates signaling dynamics, and contributes to BC growth, epithelial-to-mesenchymal transition (EMT), stemness, migration, invasion, and metastasis. We also discuss the potential of PYK2 as a therapeutic target in various BC subtypes.