Gelsolin Contributes to the Motility of A375 Melanoma Cells and This Activity Is Mediated by the Fibrous Extracellular Matrix Protein Profile

Mazurkiewicz, Ewa; Makowiecka, Aleksandra; Mrówczyńska, Ewa; Kopernyk, Iryna; Nowak, Dorota; Mazur, Antonina Joanna

doi:10.3390/cells10081848

Cited by 9 publications

(7 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 J and K). Finally, we analyzed the invasion potential of studied cells using Transwell ™ filters coated with Matrigel ™ that mimics the ECM [ 34 ]. Both ABCA1 KO and probucol-treated cells exhibited a reduced capacity for invading the ECM and migrating to the other side of the filter, which was reflected by a loss of more than 40% of invading cells when compared to scrambled and DMSO-treated cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization

Mazurkiewicz

Donizy

et al. 2023

Biol Res

Self Cite

View full text Add to dashboard Cite

Background Melanoma is one of the most aggressive and deadliest skin tumor. Cholesterol content in melanoma cells is elevated, and a portion of it accumulates into lipid rafts. Therefore, the plasma membrane cholesterol and its lateral organization might be directly linked with tumor development. ATP Binding Cassette A1 (ABCA1) transporter modulates physico-chemical properties of the plasma membrane by modifying cholesterol distribution. Several studies linked the activity of the transporter with a different outcome of tumor progression depending on which type. However, no direct link between human melanoma progression and ABCA1 activity has been reported yet. Methods An immunohistochemical study on the ABCA1 level in 110 patients-derived melanoma tumors was performed to investigate the potential association of the transporter with melanoma stage of progression and prognosis. Furthermore, proliferation, migration and invasion assays, extracellular-matrix degradation assay, immunochemistry on proteins involved in migration processes and a combination of biophysical microscopy analysis of the plasma membrane organization of Hs294T human melanoma wild type, control (scrambled), ABCA1 Knockout (ABCA1 KO) and ABCA1 chemically inactivated cells were used to study the impact of ABCA1 activity on human melanoma metastasis processes. Results The immunohistochemical analysis of clinical samples showed that high level of ABCA1 transporter in human melanoma is associated with a poor prognosis. Depletion or inhibition of ABCA1 impacts invasion capacities of aggressive melanoma cells. Loss of ABCA1 activity partially prevented cellular motility by affecting active focal adhesions formation via blocking clustering of phosphorylated focal adhesion kinases and active integrin β3. Moreover, ABCA1 activity regulated the lateral organization of the plasma membrane in melanoma cells. Disrupting this organization, by increasing the content of cholesterol, also blocked active focal adhesion formation. Conclusion Human melanoma cells reorganize their plasma membrane cholesterol content and organization via ABCA1 activity to promote motility processes and aggressiveness potential. Therefore, ABCA1 may contribute to tumor progression and poor prognosis, suggesting ABCA1 to be a potential metastatic marker in melanoma.

show abstract

Section: Resultsmentioning

confidence: 99%

ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization

Mazurkiewicz

Donizy

et al. 2023

Biol Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, the formin family member DIAPH2 [ 66 , 67 ], as well as integrin β5 (together with different α-chains) form the adhesive-protrusive domains of invadopodia [ 68 , 69 ]. It is noteworthy that gelsolin, an actin modulator associated with invadopodia [ 70 , 71 ], was elevated both transcriptionally and proteomically. The role of IDH, in invadopodia formation and matrix degradation is still unclear at the mechanistic level [ 39 ] and will require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation

et al. 2023

View full text Add to dashboard Cite

Invadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Toward that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.

show abstract

“…Published data showed that GSN played an important role in melanoma cell migration. GSN-depleted A375 melanoma cells exhibited a significantly impaired capacity to migrate on laminin, a primary component of the skin's basement membrane [34]. Changes in cellular morphology imply alteration of cell cytoskeleton proteins, including GSN that also plays an important role in cell invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Gelsolin, an Actin-Binding Protein: Bioinformatic Analysis and Functional Significance in Urothelial Bladder Carcinoma

Alsofyani,

Nedjadi

2023

IJMS

View full text Add to dashboard Cite

The involvement of the actin-regulatory protein, gelsolin (GSN), in neoplastic transformation has been reported in different cancers including bladder cancer. However, the exact mechanism by which GSN influences bladder cancer development is not well understood. Here, we sought to reveal the functional significance of GSN in bladder cancer by undertaking a comprehensive bioinformatic analysis of TCGA datasets and through the assessment of multiple biological functions. GSN expression was knocked down in bladder cancer cell lines with two siRNA isoforms targeting GSN. Proliferation, migration, cell cycle and apoptosis assays were carried out. GSN expression, enrichment analysis, protein–protein interaction and immune infiltration analysis were verified through online TCGA tools. The data indicated that GSN expression is associated with bladder cancer proliferation, migration and enhanced cell apoptosis through regulation of NF-κB expression. GSN expression correlated with various inflammatory cells and may influence the immunity of the tumor microenvironment. Computational analysis identified several interacting partners which are associated with cancer progression and patient outcome. The present results demonstrate that GSN plays an important role in bladder cancer pathogenesis and may serve as a potential biomarker and therapeutic target for cancer therapy.

show abstract

Gelsolin Contributes to the Motility of A375 Melanoma Cells and This Activity Is Mediated by the Fibrous Extracellular Matrix Protein Profile

Cited by 9 publications

References 76 publications

ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization

ABCA1 transporter promotes the motility of human melanoma cells by modulating their plasma membrane organization

Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation

Gelsolin, an Actin-Binding Protein: Bioinformatic Analysis and Functional Significance in Urothelial Bladder Carcinoma

Contact Info

Product

Resources

About