Feature Lamellipodia Filopodia
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.