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ArticleMedical oncology (Northwood, London, England)2025

Caveolae and Rho Kinase: their implication of the senescent cell morphology and the secretion of the SASP in HeLa and A549 cancer cells.

Yaprak Dilber Şimay Demir, Islam Mohammed Ahmed, Aysun Özdemir, Mustafa Ark

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Article in Medical oncology (Northwood, London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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5 · Who and what money

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4 authors.

Yaprak Dilber Şimay DemirDepartment of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye.
Islam Mohammed AhmedDepartment of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye.
Aysun ÖzdemirDepartment of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye.
Mustafa ArkDepartment of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye. mark@gazi.edu.tr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeCaveolae and Rho kinase signaling individually are both remodeled during cellular senescence and influence cell morphology and SASP secretion. However, how this interaction modulates senescent cancer-cell morphology and SASP remains unresolved. We evaluated the possible connection between caveolae and ROCK on the development of senescent cell morphology and the secretion of the SASP.

methodsSenescence was induced in HeLa and A549 cells with ouabain. Caveolin depletion was achieved with methyl-beta-cyclodextrin (MβCD) or Caveolin-1 siRNA applications. Cell morphology was assessed by cell area, volume, and thickness parameters, while SASP secretion was assessed by measuring total protein, IL-6, and VEGF-A in senescent cell secretomes. We also evaluated the effect of caveolae depletion on ROCK expression, activation, and localization.

resultsWhile the caveolae disruption with the preincubation of MβCD did not alter the occurrence of ouabain-induced senescence, it significantly altered cellular morphological features, such as decreased cell area and volume. The amount of ROCK1 and ROCK2 in the membrane fraction of cells was decreased by MβCD preincubation. These findings indicate that there may be a relationship between ROCK and the morphological changes observed in senescent cells as a result of the disruption of the caveolar structure. However, the incubation of MβCD and caveolin-1 knocking down increased the secretory activity of senescent cells. Overall secretion increases with caveolar depletion, indicating that its secretion-enhancing effect is greater than any concomitant decrease that may occur with ROCK inhibition.

conclusionThese data suggest that maintaining the integrity of caveolar structures plays a critical role in mitigating the detrimental effects of SASP released from chemotherapy-induced senescent cells.

Indexed as

CaveolaeCellular Senescencerho-Associated KinasesSenescence-Associated Secretory PhenotypeA549 CellsCaveolin 1HeLa CellsHumansOuabainCaveolin 1Ouabainrho-Associated KinasesROCK1 protein, humanROCK2 protein, humanCancerCardiac glycosideCaveolaeDrug-induced senescenceROCK

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.