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Effect of lysosomal alkalinization on nutrient-rich and nutrient-depleted Caco-2 cells

ABSTRACT: Effect of lysosomal alkalinization on nutrient-rich and nutrient-depleted Caco-2 cells

PROVIDER: PRJNA1028281 | ENA |

REPOSITORIES: ENA

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Effect of lysosomal alkalinization on nutrient-rich and nutrient-depleted Caco-2 cells

Project description:Nutrient restriction in cancer cells can activate a number of stress response pathways for cell survival. We aimed to determine mechanistically how nutrient depletion (ND) in colorectal cancer (CRC) cells leads to cellular adaptation. Caco-2 cells under ND showed high viability, tumor-forming ability, and increased expression of one or more epithelial and mesenchymal markers, suggesting the activation of partial (p)-EMT. Lysosomes are activated with ND; therefore, we incubated the ND cells with the V-ATPase inhibitor Bafilomycin A1 (ND+Baf). We observed a further increase in p-EMT markers, numerous membrane protrusions, decreased cell-cell adhesion in 3D, and increased motility in ND+Baf Caco-2 cells. The protrusions in the ND+Baf cells were primarily mediated by microtubules and enabled the relocalization of lysosomes from the perinuclear region to the periphery. Overall, our data show that ND activated p-EMT in CRC cells, which was exacerbated with lysosomal alkalinization.

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