Filamin A Orchestrates Cytoskeletal Structure, Cell Migration and Stem Cell Characteristics in Human Seminoma TCam-2 Cells

Abstract

Filamins are large dimeric F-actin cross-linking proteins, crucial for the mechanosensitive properties of a number of cell types. Due to their interaction with a variety of different proteins, they exert important regulatory functions. However, in the human testis the role of filamins has been insufficiently explored. Immunohistochemical staining of human testis samples identified filamin A (FLNA) in spermatogonia and peritubular myoid cells. Investigation of different testicular tumor samples indicated that seminoma also express FLNA. Moreover, mass spectrometric analyses identified FLNA as one of the most abundant proteins in human seminoma TCam-2 cells. We therefore focused on FLNA in TCam-2 cells, and identified by co-immunoprecipitation LAD1, RUVBL1 and DAZAP1, in addition to several cytoskeletal proteins, as interactors of FLNA. To study the role of FLNA in TCam-2 cells, we generated FLNA-deficient cells using the CRISPR/Cas9 system. Loss of FLNA causes an irregular arrangement of the actin cytoskeleton and mechanical instability, impaired adhesive properties and disturbed migratory behavior. Furthermore, transcriptional activity of typical stem cell factors is increased in the absence of FLNA. In summary, our data suggest that FLNA is crucially involved in balancing stem cell characteristics and invasive properties in human seminoma cells and possibly human testicular germ cells.

Sema3d Restrained Hepatocellular Carcinoma Progression Through Inactivating Pi3k/Akt Signaling via Interaction With FLNA

“…Previously, FLNA has been proven to regulate cytoskeleton structure and cell migration in organogenesis ( 47 ) and is also involved in multiple cellular pathways. It can be linked as an important factor in many cancer-promoting steps ( 48 ).…”

TRIP13/FLNA Complex Promotes Tumor Progression and Is Associated with Unfavorable Outcomes in Melanoma

“…FLNA, the most abundant and widely expressed member of the filamin family, functions as a nonmuscle actin filament crosslinking protein [ 28 ] to stabilize the cytoskeleton and maintain the structural integrity of cells [ 29 ]. FLNA was shown to associate with multiple functional noncytoskeletal proteins and is involved in several pathways that regulate cell migration and adhesion and promote tumor progression [ 30 ]. For example, c-Met/AKT/FLNA/SMAD formed a positive feedback loop to enhance EMT, which contributed to 5-fluorouracil resistance in CRC cells [ 31 ].…”

TRIP13 Activates the PI3K/AKT Signal Pathway to Promote Melanoma Progression by Interacting With FLNA

“…FLNA crosslinks actin laments and helps to stabilize the cytoskeleton network and supports cell integrity [31] . Several studies showed that FLNA associates with multiple functional non-cytoskeletal proteins and is involved in several unrelated pathways that regulate cell migration and adhesion and promote tumor progression [32] . Mengmeng Cheng et al demonstrated that c-Met-AKT-FLNA-smad formed a positive feedback loop to enhance EMT, which contributes to 5-FU resistance of CRC cells [33] .…”