Publications by authors named "Alice-Anais Varlet"

Metastasis is the leading cause of cancer-related deaths, yet its regulatory mechanisms are not fully understood. Small-cell lung cancer (SCLC) is the most metastatic form of lung cancer, with most patients presenting with widespread disease, making it an ideal model for studying metastasis. However, the lack of suitable preclinical models has limited such studies.

View Article and Find Full Text PDF
Article Synopsis
  • Lamin A/C is crucial for nuclear stiffness, but its effects on whole-cell mechanics have not been well studied.
  • This research combines microfluidics and theoretical analysis to quantify how alterations in lamin A/C and prelamin A accumulation affect cell mechanics.
  • The findings indicate that changes in lamin A/C lead to increased cell viscosity, suggesting that whole-cell responses to mechanical stress involve both the nucleus and cytoskeletal components, which could help in diagnosing lamin-related diseases.
View Article and Find Full Text PDF

Cells in living tissues are exposed to substantial mechanical forces and constraints imposed by neighboring cells, the extracellular matrix, and external factors. Mechanical forces and physical confinement can drive various cellular responses, including changes in gene expression, cell growth, differentiation, and migration, all of which have important implications in physiological and pathological processes, such as immune cell migration or cancer metastasis. Previous studies have shown that nuclear deformation induced by 3D confinement promotes cell contractility but can also cause DNA damage and changes in chromatin organization, thereby motivating further studies in nuclear mechanobiology.

View Article and Find Full Text PDF
Article Synopsis
  • Aberrations in nuclear size and shape can indicate cancer, but it's unclear if these changes directly cause cancer or are a side effect of tumor development.
  • The study finds that invasive breast cancer cells often have lower levels of lamin A/C, a nuclear envelope protein, driven by Akt signaling, which makes their nuclei more deformable and enhances their ability to migrate, similar to conditions during metastasis.
  • In human breast tumors, lower lamin A levels were linked to increased Akt activity and worse survival rates, suggesting that the reduction of lamin A/C may enhance both the physical and biochemical properties of cancer cells to promote metastasis.
View Article and Find Full Text PDF

Many proteins are causative for inherited partial lipodystrophies, including lamins, the essential constituents of the nuclear envelope scaffold called the lamina. By performing high throughput sequencing on a panel of genes involved in lipodystrophies, we identified a heterozygous mutation in gene (c.700C > T p.

View Article and Find Full Text PDF

The cochaperone BCL2-associated athanogene 3 (BAG3), in complex with the heat shock protein HSPB8, facilitates mitotic rounding, spindle orientation, and proper abscission of daughter cells. BAG3 and HSPB8 mitotic functions implicate the sequestosome p62/SQSTM1, suggesting a role for protein quality control. However, the interplay between this chaperone-assisted pathway and the mitotic machinery is not known.

View Article and Find Full Text PDF

The fidelity of actin dynamics relies on protein quality control, but the underlying molecular mechanisms are poorly defined. During mitosis, the cochaperone BCL2-associated athanogene 3 (BAG3) modulates cell rounding, cortex stability, spindle orientation, and chromosome segregation. Mitotic BAG3 shows enhanced interactions with its preferred chaperone partner HSPB8, the autophagic adaptor p62/SQSTM1, and HDAC6, a deacetylase with cytoskeletal substrates.

View Article and Find Full Text PDF

Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the gene, with at least 20 mutations that are considered pathogenic.

View Article and Find Full Text PDF

This study details the clinical and cellular phenotypes associated with two missense heterozygous mutations in , c.1745G > T p.(Arg582Leu), and c.

View Article and Find Full Text PDF

The small heat shock protein HSPB8 and its co-chaperone BAG3 are proposed to regulate cytoskeletal proteostasis in response to mechanical signaling in muscle cells. Here, we show that in dividing cells, the HSPB8-BAG3 complex is instrumental to the accurate disassembly of the actin-based contractile ring during cytokinesis, a process required to allow abscission of daughter cells. Silencing of HSPB8 markedly decreased the mitotic levels of BAG3 in HeLa cells, supporting its crucial role in BAG3 mitotic functions.

View Article and Find Full Text PDF

The co-chaperone BAG3, in complex with the heat shock protein HSPB8, plays a role in protein quality control during mechanical strain. It is part of a multichaperone complex that senses damaged cytoskeletal proteins and orchestrates their seclusion and/or degradation by selective autophagy. Here we describe a novel role for the BAG3-HSPB8 complex in mitosis, a process involving profound changes in cell tension homeostasis.

View Article and Find Full Text PDF