GSN (Gelsolin)

In vitro, siRNA-mediated CAPG knockdown in PANC-1 and AsPC-1 cells markedly inhibited proliferation (CCK-8 assay) and migration (wound healing assay), and significantly sensitized cells to gemcitabine-induced apoptosis. Mechanistically, CAPG knockdown was associated with reduced ERK1/2 phosphorylation and Cyclin D1 expression, and ERK1/2 inhibition phenocopied the anti-proliferative and chemosensitizing effects. Our results establish CAPG as a negative prognostic biomarker in PDAC, demonstrate its critical role in driving proliferation and migration-potentially via modulating ERK pathway activity-and highlight its promise as a therapeutic target whose inhibition can enhance chemotherapy efficacy.

We propose a framework to integrate tissue and circulating GSN biology, alongside the preanalytical and analytical standardization requirements and the necessary actions to implement GSN as an auxiliary, mechanism-based biomarker in clinical chemistry. This includes standardized measurands, commutable calibrators, multicenter validation, and positioning within low-dose lung cancer care pathways.

The inhibition of TGF-B or gelsolin prevents the change in cell morphology, and the cells remain stiff and become susceptible to immune clearance in vivo. This study identifies a novel vulnerability of dormant tumor cells that could be exploited to eliminate dormant DTCs and prevent metastatic relapse.

Gelsolin-deficient LUAD progenitors can enter dormancy but succumb to immune surveillance. Thus, quiescent LUAD metastatic progenitors undergo an atypical EMT to avert immune surveillance during TGFβ-driven metastatic dormancy.

Our results reveal the F-actin assembly is inhibited by silibinin, and this results in G2/M cell cycle arrest in human breast cancer cells, providing new ideas for anti-cancer therapies including TNBCs. Abbreviations: ABPs, actin binding proteins; ARP2, actin-related protein2; Capza1, capping actin protein of muscle Z-line subunit alpha 1; CDC2, Cell Division Cycle protein 2/CDK1, Cyclin-Dependent Kinase 1; CDKi, cyclin-dependent kinase inhibitors; CDKs, cyclin-dependent kinases; CETSA, cellular thermal shift assay; CFL1, cofilin 1; Cyto D, Cytochalasin D; DARTS, drug affinity responsive target stability; DIAPH3, diaphanous related formin 3; DMEM, Dulbecco's Modified Eagle medium; ER, estrogen receptor; F-actin, filamentous actin; FBS, fetal bovine serum; G-actin, globular actin; GSN, gelsolin; HER2, human epidermal growth factor receptor 2; LAMP1, lysosomal associated membrane protein 1; NLS, nuclear localization signal; PDB, protein data bank; PFN1, profilin 1; PR, progesterone receptor; qRT-PCR, quantitative real-time polymerase chain reaction; RT, room temperature; Sili, silibinin; si-RNAs, small interfering RNAs; TNBC, triple-negative breast cancer; VP, verteporfin; YAP, Yes-associated protein.

We can hypothesise that perinuclear GSN may be involved in perinuclear halo formation and nuclear remodeling, which are mediated by Ca2+ levels and can be altered by HPV infection. We propose the YAP/GSN ratio as a critical factor for epithelial differentiation and stress adaptation, offering a diagnostic marker for malignancy prediction.

In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with pro-tumorigenic proteins like plasma gelsolin (pGSN), with D-peptides modulating these interactions. These findings underscore DCLK1's non-kinase functions as a therapeutic target and highlight novel avenues for developing precision treatments aimed at halting cancer progression and improving patient outcomes.

These findings indicate that nuclear PD-L1 serves as a poor prognostic marker in OVCA, being associated with tumor recurrence, chemoresistance, and reduced overall survival. Targeting nuclear PD-L1 may represent a novel therapeutic strategy to improve outcomes in patients with OVCA.

GSN expression was also associated with tumor size, age, and chemotherapy sensitivity for Cisplatin, Docetaxel, Doxorubicin, Etoposide, Gemcitabine, and Vinorelbine. GSN has potential as both a prognostic and therapeutic marker in ER + breast cancer, influencing immune response and drug sensitivity. Its low expression in tumors and survival benefits suggest it can help with risk assessment and treatment decisions.

Overall, we demonstrate that GSN isoforms are produced as a mixture in melanoma cells and are not redundant in their function. Therefore, to support the well-being of melanoma cells, a mixture of GSN isoforms must be produced.

Our findings underscore the complexity of clinical presentation in amyloidosis, as multiple amyloid types can co-exist in a single individual and affect various anatomical sites. Accurate assessment of the clinical phenotype and thorough amyloid fibril typing from the target organs are essential for precise diagnosis and tailored treatment.