Activating Invasion and Metastasis Module

A conserved mechanism module for the sixth hallmark of cancer (Hanahan & Weinberg): activation of invasion and metastasis, the multistep invasion-metastasis cascade that accounts for the great majority of cancer deaths. The conserved causal chain runs from activation of an epithelial-mesenchymal transition (EMT) program - loss of E-cadherin and cell-cell junctions, acquisition of a motile, invasive mesenchymal phenotype driven by EMT transcription factors (SNAIL, SLUG, ZEB1/2, TWIST) - through local invasion across the basement membrane and stroma via matrix-degrading proteases (MMPs), into intravasation, survival in the circulation as circulating tumor cells, extravasation at a distant site, and finally metastatic colonization, the rate-limiting step in which disseminated cells adapt to the foreign microenvironment and resume proliferation (often after a period of dormancy). Individual disorder entries declare conformance via conforms_to, substituting tumor-type-specific drivers and organotropic patterns (e.g., bone-tropic breast cancer, liver-tropic colorectal cancer). This module connects to tumor_angiogenesis (vasculature provides the route for dissemination) and tumor_promoting_inflammation (stromal cells facilitate invasion).