Epithelial to Mesenchymal Transition (EMT)

Epithelial to mesenchymal transition (EMT) is critical for normal embryonic development, and aberrantly reactivated EMT mechanisms in adults contribute to pathological states such as metastasis. Growing evidence indicates that EMT mechanisms contribute to cancer stem cell (CSC) generation, suggesting that therapeutic targeting of EMT may restrict CSCs and inhibit migratory behavior associated with metastasis.

EMT Induction

Many pathways that induce EMT activate intracellular signal transduction cascades and modulate the expression of epithelial and mesenchymal cell-specific genes. Numerous signaling pathways interact to induce or inhibit EMT depending on specific cellular contexts.

Actin Stress Fibers and Focal Adhesions During EMT

Actin cytoskeleton remodeling and focal adhesion formation are associated with increased cell movement during EMT. Actin is assembled into contractile stress fibers, which are organized structures consisting of parallel actin fibers with periodic cross-linking proteins. Actin stress fiber stability is maintained by inhibition of actin depolymerization. Four stress fiber subtypes have been described based on intracellular location: ventral and dorsal stress fibers, perinuclear actin cap, and transverse arcs. 

Focal adhesions link the cytoskeleton to the extracellular matrix and allow the cell to communicate with and respond to its environment. Focal adhesions are also sites of localized signal transduction events that regulate processes such as cell proliferation, differentiation, and migration.

Extracellular Matrix Remodeling and Cell Migration During EMT

Cells that undergo EMT acquire increased migratory capabilities. For a cell to migrate to another location, it must first invade the surrounding tissue by entering through localized regions of disassembled basement membrane. Specialized regions of a cell that protrude through the basement membrane and initiate invasion under pathological conditions are termed invadopodia. The related structures, podosomes, are present in osteoclasts during the physiological process of bone remodeling. Invadopodia are actin-rich membrane protrusions that accumulate MMPs necessary for extracellular matrix (ECM) remodeling and are hypothesized to contribute to the early stages of metastasis in vivo.

Epithelial Stem Cell Transcription Factors

Cells within epithelial tissues undergo high rates of turnover and require constant renewal to maintain organ homeostasis. Tissue-resident epithelial stem cells have the capacity to self-renew and differentiate to replenish senescent or damaged cells. The balance between epithelial stem cell proliferation and cell fate determination can be regulated by specific transcription factors. Increasing evidence suggests that precise control of transcription factor expression levels can affect whether an epithelial stem cell proliferates or differentiates. Consistent with this observation, deregulated transcription factor activation is associated with uncontrolled epithelial stem cell proliferation and the progression of carcinoma.

Related Products

R&D Systems offers an extensive catalog of products and tools including features such as:

  • Validated for use with multiple cell types
  • Straightforward approaches to save time and money
  • Manufactured and tested in-house to ensure lot to lot consistency
StemXVivo® EMT Induction Media Supplement

Reliably induce EMT in vitro in only 5 days using a defined formulation.

Human EMT 3-Color Immunocytochemistry Kit

Assess EMT status in human cells using three fluorochrome-conjugated antibodies.

All Products for EMT Research

Locate antibodies, proteins, and kits for EMT research available from R&D Systems.