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Biology subjects

del Rio Hernandez, A.

Publications and source records attributed to del Rio Hernandez, A..

2 recordsLinked to original sources

Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces

Stem cells are known to sense and respond to a broad range of physical stimuli arising from their extra-cellular environment. In particular, the role of the mechanical properties (Youngs or shear modulus, viscoelasticity) of biomaterials has extensively been shown to have a significant impact on the adhesion, spreading, expansion and differentiation of stem cells. In turn, cells exert forces on their environment that can lead to striking changes in shape, size and contraction of associated tissues, and may result in mechanical disruption and functional failure. However, no study has so far correlated stem cell phenotype and biomaterials toughness. Indeed, disentangling toughness-mediated cell response from other mechanosensing processes has remained elusive as it is particularly challenging to uncouple Youngs or shear moduli from toughness, within a range relevant to cell-generated forces. In this report, we show how the design of macromolecular architecture of polymer nanosheets regulates interfacial toughness, independently to interfacial shear storage modulus, and how this, in turn, controls the expansion of mesenchymal stem cells at liquid interfaces.

bioengineering↗

SREBP1 drives KRT80-dependent cytoskeletal changes and invasive behavior in endocrine resistant ERα breast cancer

Approximately 30% of women diagnosed with ER breast cancer relapse with metastatic disease following adjuvant treatment with endocrine therapies1,2. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain (TAD)3 undergoes epigenetic reprogramming in cells that develop resistance to aromatase inhibitors (AI), leading to keratin 80 (KRT80) upregulation. In agreement, an increased number of KRT80-positive cells are observed at relapse in vivo while KRT80 expression associates with poor outcome using several clinical endpoints. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 14 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion maturation and cellular stiffening, which collectively promote cancer cell invasion. Shear-wave elasticity imaging of prospective patients shows that KRT80 levels correlate with stiffer tumors in vivo. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.

cancer biology↗