Invasion regulation of cell migration Flashcards
Cell movement stimuli
- organogenesis and morphogenesis
- wounding
- growth factors/chemoattractants
- dedifferentiation (tumours)
Determination of cell movement direction
Polarity
Stopping cell movement
Contact-inhibition motility
Mechanism of cell movement
-Uses specialised structures (focal adhesion, lamellae, filopodium)
Tumour progression
1) homeostasis
2) genetic alterations
3) hyper-proliferation
4) de-differentiation (disassembly of cell-cell contacts, loss of polarity)
5) invasion (increased motility, cleavage ECM proteins)
Tumour cell migration type: Ameoboid
-Used by lymphoma, leukaemia and SCLC
Tumour cell migration type: Mesenchymal (single cells)
-Used by fibrosarcoma, glioblastoma, anaplastic tumours
Tumour cell migration type: Mesenchymal (chains)
-Used by fibrosarcoma, glioblastoma, anaplastic tumours
Tumour cell migration type: cluster/cohorts
-Used by epithelial cancer, melanoma
Tumour cell migration type: multicellular strands/sheets
-Used by epithelial cancer, vascular tumours
Tumour cell metastasis mimic morphogenetic events
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Attachment to substratum (ECM proteins)
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Filopodia
- Structure used for motility
- Finger-like protrusions rich in actin filaments
Lamellipodia
- Structure used for motility
- Sheet-like protrusions rich in actin filaments
Remodelling of actin filaments
1) Nucleation
2) Elongation
3) Capping
4) Severing
5) Cross-linking and bundling
6) Branching
7) Gel-sol transition by actin filament severing
Nucleation
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Elongation
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Capping
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Capping proteins positive end
- Cap Z
- Gelsolin
- Fragmin/Severin
Capping proteins negative end
- Tropomodulin
- Arp complex
Severing
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Severing proteins
- Gelsolin
- ADF/Cofilin
- Fragmin/Severin
Cooperation of actin functions to generate filaments
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Cross-linking and bundling
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Cross-linking and bundling proteins
- Alpha-actinin
- Fimbrin
- Filamin
- Spectrin
- Villin
- Vinculin
Cooperation of actin functions to organise filaments
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Branching
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Branching protein
Arp complex
Gel-sol transition by actin filament severing
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Diseases caused by deregulation of actin cytoskeleton
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Participation of different actin activities during cell movement
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Lamellae protrusion
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Cell shape and actin cytoskeleton organisation
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Signalling mechanisms regulating the actin cytoskeleton
1) ion flux changes (ie: intracellular calcium)
2) phosphoinositide signalling (phospholipid binding)
3) kinases/phosphatases (phosphorylation cytoskeletal proteins)
4) signalling cascades via small GTPases
Control of actin cytoskeleton by small G proteins
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Rho family of small GTPases
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Participation of small GTPases on cell migration
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