Which mechanism allows cancer cells to resist anoikis (apoptosis triggered by loss of cell-matrix contact), facilitating metastasis?

• A Downregulation of E-cadherin reducing cell-cell adhesion
• B Upregulation of MMP-2 and MMP-9 degrading basement membrane
• C Constitutive activation of PI3K/Akt survival signaling independent of integrin engagement ✓
• D Epithelial-to-mesenchymal transition increasing migratory capacity

Explanation

Anoikis resistance is conferred primarily by constitutive activation of PI3K/Akt survival signaling (e.g., via KRAS, EGFR, or PTEN loss), which suppresses the pro-apoptotic Bim and Bad proteins without requiring integrin-matrix contact. This allows disseminated tumor cells to survive in the bloodstream and at distant sites. E-cadherin loss promotes EMT (invasion). MMP upregulation aids basement membrane degradation. EMT increases motility but is distinct from anoikis resistance.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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