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Fig. 2 | Cell Division

Fig. 2

From: Principles of dormancy evident in high-grade serous ovarian cancer

Fig. 2

Mechanisms controlling cellular dormancy in HGSOC spheroids. A HGSOC spheroid cells undergo several stress induced reprogramming events to induce cellular quiescence through p38 and ERK regulation. These lead to increased expression of CDK inhibitors, assembly of DREAM, and inhibition of CDK activity. Additional pathways contribute to the dormancy phenotype, including metabolic reprogramming via increased LKB1 and AMPK activities, decreased PI3K-AKT signaling, and the induction of macroautophagy. EMT and stemness are promoted by TGFβ and WNT signaling, respectively, and these ligands can be produced directly by HGSOC cells or by other cells within the microenvironmental niche. B HGSOC spheroids may be directly impacted by numerous different cell types of the unique microenvironment of the peritoneal cavity and malignant ascites fluid. These include tumor-associated macrophages, fibroblasts, and T-cells, all of which can provide cytokine signals or direct cell-cell contacts to impact the dormant phenotype. Spheroids directly interact with mesothelial cells on peritoneal surfaces, leading to mesothelial clearance and invasion into the underlying stroma. During this process, HGSOC cells can undergo a dormant-to-proliferative switch, as well as reverse their mesenchymal phenotype when establishing secondary tumor deposits

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