Abstract
Filamin-A (FLNA), also called actin-binding protein 280 (ABP-280), was originally identified as a non-muscle actin binding protein, which organizes filamentous actin into orthogonal networks and stress fibers. Filamin-A also anchors various transmembrane proteins to the actin cytoskeleton and provides a scaffold for a wide range of cytoplasmic and nuclear signaling proteins. Intriguingly, several studies have revealed that filamin-A associates with multiple non-cytoskeletal proteins of diverse function and is involved in several unrelated pathways. Mutations and aberrant expression of filamin-A have been reported in human genetic diseases and several types of cancer. In this review, we discuss the implications of filamin-A in cancer progression, including metastasis and DNA damage response.
Highlights
The cytoskeleton, a complex network of protein fibers in eukaryotic cells, provides a dynamic structural framework that is crucial for maintaining normal cell activity, including cell shape, cellular motion, division, and intracellular transport among other processes [1,2,3]
The importance of filamin-A controlled cell adhesion and migration in human development has been confirmed using mouse models and established cell lines of filamin-A deficiency [39,40,41,42,43]. These approaches have been successful in reconstructing the phenotypes observed in patients carrying FLNA defects, indicating that impaired filamin-A is likely responsible for several human genetic diseases
The question of whether the filamin-A levels witnessed in these cancer tissues were inclusive of surrounding extracellular matrix (ECM) among the in situ carcinoma remains elusive, this study suggests that loss of filamin-A enhances FAK turnover, which results in the disrupting cancer cell attachment to the EMC
Summary
The cytoskeleton, a complex network of protein fibers in eukaryotic cells, provides a dynamic structural framework that is crucial for maintaining normal cell activity, including cell shape, cellular motion, division, and intracellular transport among other processes [1,2,3]. Actin filaments cross-link into bundles to form the dynamic actin cytoskeletal network, which is in turn finely tuned by multiple families of cytoskeletal proteins [6], called actin binding proteins. These proteins typically share a conserved, α-actinin-like F-actin binding domain (ABD) [7,8,9]. The importance of filamin-A controlled cell adhesion and migration in human development has been confirmed using mouse models and established cell lines of filamin-A deficiency [39,40,41,42,43] These approaches have been successful in reconstructing the phenotypes observed in patients carrying FLNA defects, indicating that impaired filamin-A is likely responsible for several human genetic diseases. The conformation of Rod 2 region modulates the interaction of FLNA with multiple binding partners (Table 1), which allow the binding affinity of FLNA to actin filaments to be finely tuned to the arrangement of F-actin which varies throughout the
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