Definition |
Broad, sheet-like protrusions at the leading edge
of migrating cells, essential for cell movement. |
Thin, spike-like
protrusions from the leading edge of migrating cells, playing roles in
sensing the cellular environment and directionality. |
Key Cytoskeletal Components |
Actin filaments arranged in a
branched network, primarily regulated by the Arp2/3 complex. |
Tightly
bundled actin filaments, elongated by formins and enabled by
fascin. |
Primary Regulators |
Rac1 GTPase stimulates the Arp2/3 complex
to initiate actin polymerization. |
Cdc42 GTPase activates formins to
promote actin polymerization and bundling. |
Signaling Molecules
|
- Rac1
- Arp2/3 complex
- WAVE complex
|
- Cdc42
- Ena/VASP proteins
- Formins
|
Pathways Involved
|
Rho GTPase signaling:
- Rac1 activation leads to WAVE complex recruitment, activating the
Arp2/3 complex for actin nucleation.
PI3K/Akt signaling:
- Promotes Rac1 and Arp2/3 complex activities, enhancing lamellipodia
formation and cell migration.
- Influences the activity of proteins that control actin polymerization
and depolymerization, regulating the dynamic rearrangement of the actin
cytoskeleton for lamellipodia extension.
|
Rho GTPase and PI3K/Akt signaling:
- Cdc42 activation triggers formin-mediated actin elongation. Formins
are actin-binding proteins that nucleate the elongation of unbranched
actin filaments. The PI3K/Akt pathway can influence the activity of
formins directly or indirectly through Cdc42.
FAK-Src signaling:
- Facilitates integrin-mediated signaling, enhancing filopodia formation
for cell adhesion and migration.
|
Role in Cancer |
Lamellipodia are crucial for cancer cell
migration, invasion, and metastasis by facilitating cell movement
through the ECM. |
Filopodia contribute to cancer cell invasion and
metastasis by probing the environment, forming contacts with the ECM,
and directing migration. |
Targeted Therapies |
Inhibitors targeting Rac1 or the Arp2/3
complex to disrupt lamellipodia formation and hinder cancer cell
migration. |
Small molecules or peptides inhibiting Cdc42 activity or
formin function to prevent filopodia formation and impair metastatic
potential. |