Metastasis to lymph nodes (LNs) is a common feature of disease progression in most solid organ malignancies. Consequently, LN biopsy and lymphadenectomy are common clinical practices, not only because of their diagnostic utility but also as a means of deterring further metastatic spread. LN metastases have the potential to seed additional tissues and can induce metastatic tolerance, a process by which tumor-specific immune tolerance in LNs promotes further disease progression. Nonetheless, phylogenetic studies have revealed that distant metastases are not necessarily derived from nodal metastases. Furthermore, immunotherapy efficacy is increasingly being attributed to initiation of systemic immune responses within LNs. We argue that lymphadenectomy and nodal irradiation should be approached with caution, particularly in patients receiving immunotherapy.

Mechanobiology studies the mechanisms by which cells sense and respond to physical forces, and the role of these forces in shaping cells and tissues themselves. Mechanosensing can occur at the plasma membrane, which is directly exposed to external forces, but also in the cell's interior, for example, through deformation of the nucleus. Less is known on how the function and morphology of organelles are influenced by alterations in their own mechanical properties, or by external forces. Here, we discuss recent advances on the mechanosensing and mechanotransduction of organelles, including the endoplasmic reticulum (ER), the Golgi apparatus, the endo-lysosmal system, and the mitochondria. We highlight open questions that need to be addressed to gain a broader understanding of the role of organelle mechanobiology.

As cancer cells develop resistance to apoptosis, non-apoptotic cell death modalities, such as ferroptosis, have emerged as promising strategies to combat therapy-resistant cancers. Cells that develop resistance to conventional therapies or metastatic cancer cells have been shown to have increased sensitivity to ferroptosis. Therefore, targeting the regulatory elements of ferroptosis in cancer could offer novel therapeutic opportunities. In this review, we first provide an overview of the known ferroptosis regulatory networks and discuss recent findings on how they contribute to cancer plasticity. We then expand into the critical role of selenium metabolism in regulating ferroptosis. Finally, we highlight specific cases where induction of ferroptosis could be used to sensitize cancer cells to this form of cell death.

Acquisition of omics data advances at a formidable pace. Yet, our ability to utilize these data to control cell phenotypes and design interventions that reverse pathological states lags behind. Here, we posit that cell states are determined by core networks that control cell-wide networks. To steer cell fate decisions, core networks connecting genotype to phenotype must be reconstructed and understood. A recent method, cell state transition assessment and regulation (cSTAR), applies perturbation biology to quantify causal connections and mechanistically models how core networks influence cell phenotypes. cSTAR models are akin to digital cell twins enabling us to purposefully convert pathological states back to physiologically normal states. While this capability has a range of applications, here we discuss reverting oncogenic transformation.

Evolutionary cell biology explores the origins, principles, and core functions of cellular features and regulatory networks through the lens of evolution. This emerging field relies heavily on comparative experiments and genomic analyses that focus exclusively on extant diversity and historical events, providing limited opportunities for experimental validation. In this opinion article, we explore the potential for experimental laboratory evolution to augment the evolutionary cell biology toolbox, drawing inspiration from recent studies that combine laboratory evolution with cell biological assays. Primarily focusing on approaches for single cells, we provide a generalizable template for adapting experimental evolution protocols to provide fresh insight into long-standing questions in cell biology.

Extracellular purinergic molecules act as signaling molecules that bind to cellular receptors and regulate signaling pathways. Growing evidence suggests that purines regulate adipocyte function and whole-body metabolism. Here, we focus on one specific purine: inosine. Brown adipocytes, which are important regulators of whole-body energy expenditure (EE), release inosine when they are stressed or become apoptotic. Unexpectedly, inosine activates EE in neighboring brown adipocytes and enhances differentiation of brown preadipocytes. Increasing extracellular inosine, either directly by increasing inosine intake or indirectly via pharmacological inhibition of cellular inosine transporters, increases whole-body EE and counteracts obesity. Thus, inosine and other closely related purines might be a novel approach to tackle obesity and associated metabolic disorders by enhancing EE.

Transfer RNA (tRNA) plays a central role in translation by functioning as a biological link between messenger RNA (mRNA) and proteins. One prominent feature of the tRNA molecule is its heavily modified status, which greatly affects its biogenesis and function. Modifications within the anticodon loop are crucial for translation efficiency and accuracy, whereas other modifications in the body region affect tRNA structure and stability. Recent research has revealed that these diverse modifications are critical regulators of gene expression. They are involved in many important physiological and pathological processes, including cancers. In this review we focus on six different tRNA modifications to delineate their functions and mechanisms in tumorigenesis and tumor progression, providing insights into their clinical potential as biomarkers and therapeutic targets.