Volume 8 (2024)

MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression

Zhao Lin1, Megan E. Roche1, Víctor Díaz-Barros1, Marina Domingo-Vidal2, Diana Whitaker-Menezes1, Madalina Tuluc3, Guldeep Uppal3, Jaime Caro4, Joseph M. Curry5 and Ubaldo Martinez-Outschoorn1

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces (...)

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Cold exposure reinstates NAD+ levels and attenuates hepatocellular carcinoma

Tatiana P Grazioso1,2,3, Maria del Mar Rigual1, Cristian Perna4,5, Eduardo J Caleiras6 and Nabil Djouder1

INTRODUCTION Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor that arises from hepatocytes, the main functional cells of the liver 1. It is a leading cause

Endogenous plasma resuspension of peripheral blood mononuclear cells prevents preparative-associated stress that modifies polyA-enriched RNA responses to subsequent acute stressors

Dongyang Li1,2, Karina Al-Dahleh1,2, Daniel A Murphy2,3, Sonya Georgieva1, Nik Matthews4 and Claire L Shovlin1,2,5,*

INTRODUCTION Cells are impacted by complex and co-occurring stresses throughout a life-course. Our goal was to generate physiologically relevant models of acute cellular stress, initially in relation to 3’ untranslated

Neuroglobin-enriched secretome provides neuroprotection against hydrogen peroxide and mitochondrial toxin-induced cellular stress

Giovanna Bastari1,a, Virginia Solar Fernandez1,2,a, Maurizio Muzzi3,4, Sandra Moreno3,5, Maria Marino1,5 and Marco Fiocchetti1,5

INTRODUCTION Cellular response to stress relies on evolutionary conserved mechanisms aimed at maintaining homeostasis and facilitating adaptation to new cellular environments 1. Under stressful conditions, post-mitotic neurons are hardly replaced.

Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure

Hebatallah Abdelrasol1,a, Avika Chopra1,a, Liana Shvachiy1, Dirk Beutner2, Tiago F Outeiro1,3,4,5,* and Cristian Setz2,1,*

INTRODUCTION Cellular stress is an inherent and inevitable aspect of cell physiology, prompting cells to adapt to environmental changes. Among the distinctive intracellular adaptive responses that have been characterized in

Dynamics of cell membrane lesions and adaptive conductance under the electrical stress

Mantas Silkunas, Olga N Pakhomova, Giedre Silkuniene and Andrei G. Pakhomov

Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca2+ entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a low 50- to 300-pS conductance, which disappeared instantly once the hyperpolarization was removed. Charging to - 240 mV created high-conductance (> 1 nS) pores which persisted for seconds even at zero membrane potential. With (...)

Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment

Vincent Géli and Norbert Nabet

INTRODUCTION The possibility of using biological fluids such as blood, urine, saliva and other biofluids to diagnose pathologies is a relatively old idea that has taken on a new lease

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Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment

Vincent Géli and Norbert Nabet

INTRODUCTION The possibility of using biological fluids such as blood, urine, saliva and other biofluids to diagnose pathologies is a relatively old idea that has taken on a new lease

CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis?

Ziyuan Guo1,#, Yang Chen1,#, Yaran Wu1 and Jiqin Lian1

Metastasis is the leading cause of death in cancer patients. Currently, there are no effective treatments to prevent cancer metastases. Therefore, it is imperative to provide more effective biomarkers and

Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome

Lucille Ferret1,2,3, Guido Kroemer1,2,4 and Mojgan Djavaheri-Mergny1,2

Mechanistic target of rapamycin complex 1 (mTORC1) is a multiprotein complex that serves as a pivotal regulator of cell growth, protein synthesis, metabolism and autophagy [1][2]. This complex compromises mTOR

The missing hallmark of health: psychosocial adaptation

Carlos López-Otín1,2,3 and Guido Kroemer1,4,5

INTRODUCTION The comprehension of health –defined in a positive fashion rather than as the absence of disease–requires a theory. We recently launched the bases of such a health theory by