This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "invasion_and_metastasis#Local Invasion and Intravasation" or "invasion_and_metastasis#Metastatic Colonization"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding cell types, biological processes, and causal edges, specialized to their tumor context. Key tumor-specific substitutions: carcinomas use classical E-cadherin-loss EMT; organotropism (Paget "seed and soil") substitutes the target organ and its premetastatic niche. Key conformance target: "invasion_and_metastasis#Metastatic Colonization".
Epithelial-Mesenchymal Transition Activation
trigger
Tumor cells reactivate the latent embryonic EMT program. EMT transcription factors (SNAIL, SLUG, ZEB1/2, TWIST), induced by TGF-beta, Wnt, and signals from the tumor stroma, repress E-cadherin and other epithelial genes and induce mesenchymal markers. Cells lose apical-basal polarity and cell-cell adhesion and acquire a motile, invasive phenotype. EMT is typically partial and reversible (epithelial-mesenchymal plasticity), enabling later reversion (MET) at the metastatic site.
Downstream
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Local Invasion and Intravasation
Show evidence (1 reference)
"the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view"
Frames the cellular programs (including EMT) that drive dissemination and metastatic outgrowth, the trigger of this module. Evidence source is OTHER because this is a review article.
Local Invasion and Intravasation
effector
Motile tumor cells invade locally, degrading the basement membrane and extracellular matrix with matrix metalloproteinases and other proteases and migrating through the stroma, often led by invadopodia and aided by tumor-associated macrophages and cancer-associated fibroblasts. Invading cells reach and penetrate the walls of blood or lymphatic vessels (intravasation), entering the circulation.
Used by disorders
Choriocarcinoma
as Deregulated Trophoblast Invasion and Vascular Permeation
Downstream
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Circulatory Survival and Extravasation
Circulatory Survival and Extravasation
effector
As circulating tumor cells, disseminating cells must survive loss of matrix attachment (resisting anoikis), shear stress, and immune surveillance, sometimes shielded by platelet cloaking. Surviving cells arrest in the microvasculature of a distant organ and extravasate across the endothelium into the parenchyma, a step shaped by organ-specific adhesion and chemokine cues.