Intermediate filaments: Integration of cell mechanical properties during migration

Infante, Elvira; Etienne‐Manneville, Sandrine

doi:10.3389/fcell.2022.951816

Cited by 14 publications

(7 citation statements)

References 112 publications

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“…This discovery broadens the known genetic spectrum of KRT4 mutations associated with WSN. The primary roles of KRT include maintaining cellular integrity, facilitating intercellular adhesion, and participating in intracellular signal transmission, material transport, and cell differentiation [ 13 , 14 ]. Altered expression patterns of KRT during and post-malignant transformation have been reported to influence various signaling pathways implicated in tumor progression [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation

Liu,

Zhang,

Zhou

et al. 2024

BMC Oral Health

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Background White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN. Case presentation We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion. Conclusions This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation

Liu,

Zhang,

Zhou

et al. 2024

BMC Oral Health

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“…Notably, recent studies have demonstrated that vimentin, which contributes to cells resilience against mechanical stress [ 54 ], generates with actin and microtubules the forces required for cell adhesion. More specifically, vimentin regulates stress generation by adherent cells through an interplay with actin stress fibers [ 55 ]. We can speculate that alteration of the mechanical forces within the glomerulus in vivo may lead to cytoskeleton alterations and the detachment of renal progenitors from the basement membrane.…”

Section: Discussionmentioning

confidence: 99%

Modeled microgravity unravels the roles of mechanical forces in renal progenitor cell physiology

Melica,

Cialdai,

La Regina

et al. 2024

Stem Cell Res Ther

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Background The glomerulus is a highly complex system, composed of different interdependent cell types that are subjected to various mechanical stimuli. These stimuli regulate multiple cellular functions, and changes in these functions may contribute to tissue damage and disease progression. To date, our understanding of the mechanobiology of glomerular cells is limited, with most research focused on the adaptive response of podocytes. However, it is crucial to recognize the interdependence between podocytes and parietal epithelial cells, in particular with the progenitor subset, as it plays a critical role in various manifestations of glomerular diseases. This highlights the necessity to implement the analysis of the effects of mechanical stress on renal progenitor cells. Methods Microgravity, modeled by Rotary Cell Culture System, has been employed as a system to investigate how renal progenitor cells respond to alterations in the mechanical cues within their microenvironment. Changes in cell phenotype, cytoskeleton organization, cell proliferation, cell adhesion and cell capacity for differentiation into podocytes were analyzed. Results In modeled microgravity conditions, renal progenitor cells showed altered cytoskeleton and focal adhesion organization associated with a reduction in cell proliferation, cell adhesion and spreading capacity. Moreover, mechanical forces appeared to be essential for renal progenitor differentiation into podocytes. Indeed, when renal progenitors were exposed to a differentiative agent in modeled microgravity conditions, it impaired the acquisition of a complex podocyte-like F-actin cytoskeleton and the expression of specific podocyte markers, such as nephrin and nestin. Importantly, the stabilization of the cytoskeleton with a calcineurin inhibitor, cyclosporine A, rescued the differentiation of renal progenitor cells into podocytes in modeled microgravity conditions. Conclusions Alterations in the organization of the renal progenitor cytoskeleton due to unloading conditions negatively affect the regenerative capacity of these cells. These findings strengthen the concept that changes in mechanical cues can initiate a pathophysiological process in the glomerulus, not only altering podocyte actin cytoskeleton, but also extending the detrimental effect to the renal progenitor population. This underscores the significance of the cytoskeleton as a druggable target for kidney diseases.

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“…Intermediate filaments, including nuclear lamins and vimentins, are connected to other cytoskeletal elements through the LINC complex and binding proteins like plectin. Therefore, intermediate filaments may also play a role in mechanotransduction, but their molecular mechanism is less explored compared to other cytoskeletal components [248].…”

Section: Cell and Tissue Mechanics In Normal And Aberrant Physiologymentioning

confidence: 99%

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

Nakamura

2024

IJMS

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Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

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Intermediate filaments: Integration of cell mechanical properties during migration

Cited by 14 publications

References 112 publications

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation

Modeled microgravity unravels the roles of mechanical forces in renal progenitor cell physiology

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

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