Pathology · Advanced Pathology Mechanisms (Multi-topic)

During the process of EMT (epithelial-to-mesenchymal transition) in cancer invasion, E-cadherin expression is silenced. Which transcription factors drive E-cadherin repression in EMT?

  • A SNAIL1, TWIST1, and ZEB1/2 (zinc-finger and basic helix-loop-helix repressors)
  • B SOX2, OCT4, and NANOG (pluripotency factors)
  • C c-MYC and MYCN (basic helix-loop-helix activators)
  • D HIF-2alpha and STAT3 (hypoxia-induced transcription factors)
Correct answer: A. SNAIL1, TWIST1, and ZEB1/2 (zinc-finger and basic helix-loop-helix repressors)

Explanation

EMT is orchestrated by a network of transcription factors, principally SNAIL1/2 (Snail superfamily zinc-finger), TWIST1/2 (basic helix-loop-helix), and ZEB1/2 (zinc-finger E-box binding). These factors bind E-box elements in the CDH1 (E-cadherin) promoter and recruit repressor complexes (HDAC, PRC2) to silence CDH1 transcription, leading to loss of E-cadherin, disruption of adherens junctions, and acquisition of mesenchymal markers (vimentin, fibronectin, N-cadherin). SOX2/OCT4/NANOG maintain pluripotency in stem cells. c-MYC drives proliferation. HIF-2alpha/STAT3 contribute to some aspects of EMT but are not the defining CDH1 repressors.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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