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Pekka Lappalainen - One of the best experts on this subject based on the ideXlab platform.
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actin depolymerizing factor and Cofilin 1 play overlapping roles in promoting rapid f actin depolymerization in mammalian nonmuscle cells
Molecular Biology of the Cell, 2004Co-Authors: Pirta Hotulainen, Eija Paunola, Maria K. Vartiainen, Pekka LappalainenAbstract:Actin-depolymerizing factor (ADF)/Cofilins are small actin-binding proteins found in all eukaryotes. In vitro, ADF/Cofilins promote actin dynamics by depolymerizing and severing actin filaments. However, whether ADF/Cofilins contribute to actin dynamics in cells by disassembling “old” actin filaments or by promoting actin filament assembly through their severing activity is a matter of controversy. Analysis of mammalian ADF/Cofilins is further complicated by the presence of multiple isoforms, which may contribute to actin dynamics by different mechanisms. We show that two isoforms, ADF and Cofilin-1, are expressed in mouse NIH 3T3, B16F1, and Neuro 2A cells. Depleting Cofilin-1 and/or ADF by siRNA leads to an accumulation of F-actin and to an increase in cell size. Cofilin-1 and ADF seem to play overlapping roles in cells, because the knockdown phenotype of either protein could be rescued by overexpression of the other one. Cofilin-1 and ADF knockdown cells also had defects in cell motility and cytokinesis, and these defects were most pronounced when both ADF and Cofilin-1 were depleted. Fluorescence recovery after photobleaching analysis and studies with an actin monomer-sequestering drug, latrunculin-A, demonstrated that these phenotypes arose from diminished actin filament depolymerization rates. These data suggest that mammalian ADF and Cofilin-1 promote cytoskeletal dynamics by depolymerizing actin filaments and that this activity is critical for several processes such as cytokinesis and cell motility.
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cyclase associated protein 1 cap1 promotes Cofilin induced actin dynamics in mammalian nonmuscle cells
Molecular Biology of the Cell, 2004Co-Authors: Enni Bertling, Pieta K Mattila, Pirta Hotulainen, Tanja Matilainen, Marjo Salminen, Pekka LappalainenAbstract:Cyclase-associated proteins (CAPs) are highly conserved actin monomer binding proteins present in all eukaryotes. However, the mechanism by which CAPs contribute to actin dynamics has been elusive. In mammals, the situation is further complicated by the presence of two CAP isoforms whose differences have not been characterized. Here, we show that CAP1 is widely expressed in mouse nonmuscle cells, whereas CAP2 is the predominant isoform in developing striated muscles. In cultured NIH3T3 and B16F1 cells, CAP1 is a highly abundant protein that colocalizes with Cofilin-1 to dynamic regions of the cortical actin cytoskeleton. Analysis of CAP1 knockdown cells demonstrated that this protein promotes rapid actin filament depolymerization and is important for cell morphology, migration, and endocytosis. Interestingly, depletion of CAP1 leads to an accumulation of Cofilin-1 into abnormal cytoplasmic aggregates and to similar cytoskeletal defects to those seen in Cofilin-1 knockdown cells, demonstrating that CAP1 is required for proper subcellular localization and function of ADF/Cofilin. Together, these data provide the first direct in vivo evidence that CAP promotes rapid actin dynamics in conjunction with ADF/Cofilin and is required for several central cellular processes in mammals.
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the three mouse actin depolymerizing factor Cofilins evolved to fulfill cell type specific requirements for actin dynamics
Molecular Biology of the Cell, 2002Co-Authors: Maria K. Vartiainen, Pieta K Mattila, Pauli J Ojala, Irma Thesleff, Tuija Mustonen, Juha Partanen, Pekka LappalainenAbstract:Actin-depolymerizing factor (ADF)/Cofilins are essential regulators of actin filament turnover. Several ADF/Cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/Cofilins exist in mouse and most likely in all other mammalian species. Northern blot and in situ hybridization analyses demonstrate that Cofilin-1 is expressed in most cell types of embryos and adult mice. Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia. Although the three mouse ADF/Cofilins do not show actin isoform specificity, they all depolymerize platelet actin filaments more efficiently than muscle actin. Furthermore, these ADF/Cofilins are biochemically different. The epithelial-specific ADF is the most efficient in turning over actin filaments and promotes a stronger pH-dependent actin filament disassembly than the two other isoforms. The muscle-specific Cofilin-2 has a weaker actin filament depolymerization activity and displays a 5-10-fold higher affinity for ATP-actin monomers than Cofilin-1 and ADF. In steady-state assays, Cofilin-2 also promotes filament assembly rather than disassembly. Taken together, these data suggest that the three biochemically distinct mammalian ADF/Cofilin isoforms evolved to fulfill specific requirements for actin filament dynamics in different cell types.
Perumal Thiagarajan - One of the best experts on this subject based on the ideXlab platform.
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Cofilin 1 induced actin reorganization in stored platelets
Transfusion, 2020Co-Authors: Swapan K Dasgupta, Perumal ThiagarajanAbstract:BACKGROUND During platelet storage, there are extensive changes in cytoskeleton and phosphatidylserine exposure. The intrinsic mitochondrial pathway of apoptosis, activated in stored platelets, is a major mediator these changes. Cofilin-1 is an effector of actin reorganization. We examined the effect of Cofilin-1 deficiency on cytoskeleton and phosphatidylserine exposure during storage and following activation of apoptosis. METHODS AND RESULTS We assessed actin filaments by Alexa-647-phalloidin and phosphatidylserine exposure by fluorescein isothiocyanate-lactadherin by fluorescence microscopy. In fresh platelets, actin filaments are distributed in the subcortical region, and they do not express phosphatidylserine in the outer surface. In stored platelets, there is retraction of actin filaments from the subcortical region with increased phosphatidylserine expression. These changes are seen in 20% of platelets of 6 days old and increases further with storage. Treatment with ABT-737, which activates the mitochondrial apoptosis, induces similar cytoskeletal changes in actin filaments with increased phosphatidylserine. Cofilin-1 is activated in stored platelets as well as in ABT-737 treated platelets by dephosphorylation. In Cofilin-1 deficient murine platelets actin filaments are abnormal and ABT-737 induces less phosphatidylserine. Despite these changes in vitro, platelet survival of Cofilin-1 deficient platelets in mice was not significantly different from their wild-type controls. CONCLUSION These results show that Cofilin-1 plays a role in apoptosis-induced actin rearrangement and phosphatidylserine exposure during storage. Despite the defects in platelet cytoskeleton and phosphatidylserine exposure in Cofilin-1-deficient platelets, the in vivo life span of platelets is similar to littermate controls, indicating multiple redundant pathways for the clearance of platelets in vivo.
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Cofilin 1 induced actin reorganization and phosphatidylserine exposure in platelets
Blood, 2014Co-Authors: Swapan K Dasgupta, Sandra B Haudek, Mark L Entman, Perumal ThiagarajanAbstract:Abstract Background: Platelet activation leads to the transbilayer movement of phosphatidylserine (PS) from inner to the outer leaflet of membrane bilayer. Exteriorization of PS promotes platelet procoagulant activity by promoting the assembly of tenase and the prothrombinase complex on platelet membrane. In a previous study, we observed that Rho-associated coiled-coil kinase-1 (ROCK1) deficiency in murine platelets or ROCK inhibition by Y-27632 in human platelets resulted in increase in PS exposure and platelet procoagulant activity. ROCK1 deficient platelets had a marked decrease in phosphorylation of Cofilin-1. Cofilin-1 decreases actin filament length by increasing the rate of dissociation of actin monomers and its activity is abolished by phosphorylation. These studies suggested a role for Cofilin-1-induced actin reorganization in collagen-induced PS exposure. Cofilin-1 activity is also modulated by its interactions with phosphatidylinositol 4, 5-bisphosphate (PIP2) and a Cofilin-1 binding protein, Wdr1, which enhances capacity of Cofilin-1 to accelerate depolymerization by capping their barbed ends. Here, we studied the role of Cofilin-1 phosphorylation and its interaction with PIP2 and Wdr1 in activation induced PS exposure in platelets. Materials and Methods: We isolated platelet membrane, cytosol and cytoskeleton through differential centrifugation from resting and collagen-stimulated platelets and assessed the relative abundance of Cofilin-1 and phosphoCofilin-1 by mobility shift in phosphate-affinity polyacrylamide gel electrophoresis. This method allows simultaneous detection of relative proportions of phosphoproteins and its nonphospho counterparts. For Cofilin-1 and Wdr-1 distribution, platelets were immobilized on a polylysine-coated cover slip or on a collagen-coated cover slip, fixed, permeabilized and immunostained with appropriate antibody. In addition, PS exposure (FITC lactadherin binding), F-actin (Alexa Fluor 488-phalloidin) and calcium concentration (Fura-2AM fluorescence) were also measured. Results: Immunofluorescence images show that in resting platelets, Cofilin-1 is present in distinct patches in the plasma membrane and following activation with collagen, Cofilin-1 is redistributed in a discrete granular pattern throughout the cytoplasm. In parallel, we also studied the relative distribution and the phosphorylation status of Cofilin-1 in various subcellular fractions of platelets. In resting platelets, Cofilin-1 is present in the plasma membrane and in the cytosol but absent in the cytoskeleton. Following activation with collagen, Cofilin-1 moves to the cytoskeleton with a concomitant decrease in the plasma membrane fraction. These results suggest that active Cofilin-1 is incorporated into reorganizing actin cytoskeleton during platelet activation. In ROCK1-deficient mice, there is increased Cofilin-1 in cytoskeletal fraction, which also correlates with increase in PS exposure. Blocking PIP2 hydrolysis by U73122 prevents Cofilin-1 translocation and PS exposure. A cell permeable Cofilin-1 peptide containing the actin binding site of Cofilin-1 (amino acids Trp104 to Met115) at the carboxy terminus (that competitively inhibits Cofilin-1 binding to F-actin), blocks Cofilin-1 translocation and decreases PS exposure. Platelets from a Wdr1-deficient mice which express less than 2% of wild-type protein in platelets, showed impaired collagen-induced PS exposure despite equivalent increase in intra platelet calcium compared to wild-type platelets. Conclusion: Our results show Cofilin-1 trafficking from membranre to cytoskeleton and subsequent actin reorganization precedes PS exposure during platelet activation. In ROCK1-deficient platelets, there is increased Cofilin-1 activity due to decreased serine-3 phosphorylation and it is associated with increased Cofilin-1 translocation to actin filaments and enhanced PS exposure. In contrast, inhibiting Cofilin-1 translocation, either by inhibiting PIP2 hydrolysis or by competitive inhibition by a cell permeable peptide, prevents Cofilin-1 trafficking and decreases PS exposure. Furthermore, in Wdr1-deficient mouse platelets, which have diminished Cofilin-1 activity, have impaired PS exposure during platelet activation. Disclosures No relevant conflicts of interest to declare.
Swapan K Dasgupta - One of the best experts on this subject based on the ideXlab platform.
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Cofilin 1 induced actin reorganization in stored platelets
Transfusion, 2020Co-Authors: Swapan K Dasgupta, Perumal ThiagarajanAbstract:BACKGROUND During platelet storage, there are extensive changes in cytoskeleton and phosphatidylserine exposure. The intrinsic mitochondrial pathway of apoptosis, activated in stored platelets, is a major mediator these changes. Cofilin-1 is an effector of actin reorganization. We examined the effect of Cofilin-1 deficiency on cytoskeleton and phosphatidylserine exposure during storage and following activation of apoptosis. METHODS AND RESULTS We assessed actin filaments by Alexa-647-phalloidin and phosphatidylserine exposure by fluorescein isothiocyanate-lactadherin by fluorescence microscopy. In fresh platelets, actin filaments are distributed in the subcortical region, and they do not express phosphatidylserine in the outer surface. In stored platelets, there is retraction of actin filaments from the subcortical region with increased phosphatidylserine expression. These changes are seen in 20% of platelets of 6 days old and increases further with storage. Treatment with ABT-737, which activates the mitochondrial apoptosis, induces similar cytoskeletal changes in actin filaments with increased phosphatidylserine. Cofilin-1 is activated in stored platelets as well as in ABT-737 treated platelets by dephosphorylation. In Cofilin-1 deficient murine platelets actin filaments are abnormal and ABT-737 induces less phosphatidylserine. Despite these changes in vitro, platelet survival of Cofilin-1 deficient platelets in mice was not significantly different from their wild-type controls. CONCLUSION These results show that Cofilin-1 plays a role in apoptosis-induced actin rearrangement and phosphatidylserine exposure during storage. Despite the defects in platelet cytoskeleton and phosphatidylserine exposure in Cofilin-1-deficient platelets, the in vivo life span of platelets is similar to littermate controls, indicating multiple redundant pathways for the clearance of platelets in vivo.
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Cofilin 1 induced actin reorganization and phosphatidylserine exposure in platelets
Blood, 2014Co-Authors: Swapan K Dasgupta, Sandra B Haudek, Mark L Entman, Perumal ThiagarajanAbstract:Abstract Background: Platelet activation leads to the transbilayer movement of phosphatidylserine (PS) from inner to the outer leaflet of membrane bilayer. Exteriorization of PS promotes platelet procoagulant activity by promoting the assembly of tenase and the prothrombinase complex on platelet membrane. In a previous study, we observed that Rho-associated coiled-coil kinase-1 (ROCK1) deficiency in murine platelets or ROCK inhibition by Y-27632 in human platelets resulted in increase in PS exposure and platelet procoagulant activity. ROCK1 deficient platelets had a marked decrease in phosphorylation of Cofilin-1. Cofilin-1 decreases actin filament length by increasing the rate of dissociation of actin monomers and its activity is abolished by phosphorylation. These studies suggested a role for Cofilin-1-induced actin reorganization in collagen-induced PS exposure. Cofilin-1 activity is also modulated by its interactions with phosphatidylinositol 4, 5-bisphosphate (PIP2) and a Cofilin-1 binding protein, Wdr1, which enhances capacity of Cofilin-1 to accelerate depolymerization by capping their barbed ends. Here, we studied the role of Cofilin-1 phosphorylation and its interaction with PIP2 and Wdr1 in activation induced PS exposure in platelets. Materials and Methods: We isolated platelet membrane, cytosol and cytoskeleton through differential centrifugation from resting and collagen-stimulated platelets and assessed the relative abundance of Cofilin-1 and phosphoCofilin-1 by mobility shift in phosphate-affinity polyacrylamide gel electrophoresis. This method allows simultaneous detection of relative proportions of phosphoproteins and its nonphospho counterparts. For Cofilin-1 and Wdr-1 distribution, platelets were immobilized on a polylysine-coated cover slip or on a collagen-coated cover slip, fixed, permeabilized and immunostained with appropriate antibody. In addition, PS exposure (FITC lactadherin binding), F-actin (Alexa Fluor 488-phalloidin) and calcium concentration (Fura-2AM fluorescence) were also measured. Results: Immunofluorescence images show that in resting platelets, Cofilin-1 is present in distinct patches in the plasma membrane and following activation with collagen, Cofilin-1 is redistributed in a discrete granular pattern throughout the cytoplasm. In parallel, we also studied the relative distribution and the phosphorylation status of Cofilin-1 in various subcellular fractions of platelets. In resting platelets, Cofilin-1 is present in the plasma membrane and in the cytosol but absent in the cytoskeleton. Following activation with collagen, Cofilin-1 moves to the cytoskeleton with a concomitant decrease in the plasma membrane fraction. These results suggest that active Cofilin-1 is incorporated into reorganizing actin cytoskeleton during platelet activation. In ROCK1-deficient mice, there is increased Cofilin-1 in cytoskeletal fraction, which also correlates with increase in PS exposure. Blocking PIP2 hydrolysis by U73122 prevents Cofilin-1 translocation and PS exposure. A cell permeable Cofilin-1 peptide containing the actin binding site of Cofilin-1 (amino acids Trp104 to Met115) at the carboxy terminus (that competitively inhibits Cofilin-1 binding to F-actin), blocks Cofilin-1 translocation and decreases PS exposure. Platelets from a Wdr1-deficient mice which express less than 2% of wild-type protein in platelets, showed impaired collagen-induced PS exposure despite equivalent increase in intra platelet calcium compared to wild-type platelets. Conclusion: Our results show Cofilin-1 trafficking from membranre to cytoskeleton and subsequent actin reorganization precedes PS exposure during platelet activation. In ROCK1-deficient platelets, there is increased Cofilin-1 activity due to decreased serine-3 phosphorylation and it is associated with increased Cofilin-1 translocation to actin filaments and enhanced PS exposure. In contrast, inhibiting Cofilin-1 translocation, either by inhibiting PIP2 hydrolysis or by competitive inhibition by a cell permeable peptide, prevents Cofilin-1 trafficking and decreases PS exposure. Furthermore, in Wdr1-deficient mouse platelets, which have diminished Cofilin-1 activity, have impaired PS exposure during platelet activation. Disclosures No relevant conflicts of interest to declare.
Kaio Kitazato - One of the best experts on this subject based on the ideXlab platform.
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dysregulation of Cofilin 1 activity the missing link between herpes simplex virus type 1 infection and alzheimer s disease
Critical Reviews in Microbiology, 2020Co-Authors: Yiliang Wang, Xiaowei Song, Yun Wang, Lianzhou Huang, Weisheng Luo, Shurong Qin, Yuan Wang, Ji Xiao, Fujun Jin, Kaio KitazatoAbstract:Alzheimer's disease (AD) is a multifactorial disease triggered by environmental factors in combination with genetic predisposition. Infectious agents, in particular herpes simplex virus type 1 (HSV-1), are gradually being recognised as important factors affecting the development of AD. However, the mechanism linking HSV-1 and AD remains unknown. Of note, HSV-1 manipulates the activity of Cofilin-1 to ensure their efficient infection in neuron cells. Cofilin-1, the main regulator of actin cytoskeleton reorganization, is implicating for the plastic of dendritic spines and axon regeneration of neuronal cells. Moreover, dysfunction of Cofilin-1 is observed in most AD patients, as well as in mice with AD and ageing. Further, inhibition of Cofilin-1 activity ameliorates the host cognitive impairment in an animal model of AD. Together, dysregulation of Cofilin-1 led by HSV-1 infection is a potential link between HSV-1 and AD. Herein, we critically summarize the role of Cofilin-1-mediated actin dynamics in both HSV-1 infection and AD, respectively. We also propose several hypotheses regarding the connecting roles of Cofilin-1 dysregulation in HSV-1 infection and AD. Our review provides a foundation for future studies targeting individuals carrying HSV-1 in combination with Cofilin-1 to promote a more individualised approach for treatment and prevention of AD.
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Cofilin 1 is involved in regulation of actin reorganization during influenza a virus assembly and budding
Biochemical and Biophysical Research Communications, 2014Co-Authors: Ge Liu, Yangfei Xiang, Chaowan Guo, Ying Pei, Yifei Wang, Kaio KitazatoAbstract:Influenza A virus (IAV) assembly and budding on host cell surface plasma membrane requires actin cytoskeleton reorganization. The underlying molecular mechanism involving actin reorganization remains unclarified. In this study, we found that the natural antiviral compound petagalloyl glucose (PGG) inhibits F-actin reorganization in the host cell membrane during the late stage of IAV infection, which are associated with the suppression of total Cofilin-1 level and its phosphorylation. Knock-down of Cofilin-1 reduces viral yields. These findings provide the first evidence that Cofilin-1 plays an important role in regulating actin reorganization during IAV assembly and budding.
Fabio Klamt - One of the best experts on this subject based on the ideXlab platform.
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Cofilin 1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
Oncotarget, 2018Co-Authors: Candelaria Bracalente, Fabio Klamt, Adriana Rinflerch, Irene L Ibanez, Francisco M Garcia, Victoria Volonteri, Gaston Galimberti, Hebe DuranAbstract:Melanoma is an aggressive cancer with highly metastatic ability. We propose Cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined Cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher Cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI 2 vs MM with BI<2, MIS and nevi. In conclusion, an association of Cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of Cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.
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potential crosstalk between Cofilin 1 and egfr pathways in cisplatin resistance of non small cell lung cancer
Oncotarget, 2015Co-Authors: Carolina Beatriz Muller, Matheus Becker, Marco Antonio De Bastiani, Mauro A A Castro, Fernanda Stapenhorst Franca, Mariane Branco, Fabio KlamtAbstract:// Carolina Beatriz Muller 1,2,* , Marco Antonio De Bastiani 1,2,* , Matheus Becker 1,2 , Fernanda Stapenhorst Franca 1,2 , Mariane Araujo Branco 1,2 , Mauro Antonio Alves Castro 3 and F a bio Klamt 1,2 1 Laboratory of Cellular Biochemistry, Department of Biochemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil 2 National Institutes for Science & Technology-Translational Medicine (INCT-TM), Porto Alegre (RS), Brazil 3 Programa de Pos-Graduacao em Bioinformatica, Federal University of Parana (UFPR), Curitiba (PR), Brazil * These authors contributed equally to this work Correspondence to: Fabio Klamt, email: // Keywords : NSCLC, EGFR, Cofilin-1, chemotherapy resistance, personalized medicine Received : December 02, 2014 Accepted : January 22, 2015 Published : February 28, 2015 Abstract Current challenge in oncology is to establish the concept of personalized medicine in clinical practice. In this context, non-small-cell lung cancer (NSCLC) presents clinical, histological and molecular heterogeneity, being one of the most genomically diverse of all cancers. Recent advances added Epidermal Growth Factor Receptor (EGFR) as a predictive biomarker for patients with advanced NSCLC. In tumors with activating EGFR mutations, tyrosine kinase inhibitors (TKI) are indicated as first-line treatment, although restricted to a very small target population. In this context, Cofilin-1 (a cytosolic protein involved with actin dynamics) has been widely studied as a biomarker of an aggressive phenotype in tumors, and overexpression of Cofilin-1 is associated with cisplatin resistance and poor prognosis in NSCLC. Here, we gather information about the predictive potential of Cofilin-1 and reviewed the crosstalk between Cofilin-1/EGFR pathways. We aimed to highlight new perspectives of how these interactions might affect cisplatin resistance in NSCLC. We propose that Cofilin-1 quantification in clinical samples in combination with presence/absence of EGFR mutation could be used to select patients that would benefit from TKI’s treatment. This information is of paramount importance and could result in a possibility of guiding more effective treatments to NSCLC patients.
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Cofilin actin rod formation by dysregulation of Cofilin 1 activity as a central initial step in neurodegeneration
Mini-reviews in Medicinal Chemistry, 2014Co-Authors: Patricia Schonhofen, Liana Marengo De Medeiros, Carolina Piletti Chatain, Ivi Juliana Bristot, Fabio KlamtAbstract:Cofilin-1 protein, which main function is to regulate actin cytoskeleton dynamics, appears to be involved with many steps in the neurotoxicity processes found in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the dynamics of actin filaments play a major role in several cellular processes, the primary involvement of Cofilin-1 dysfunctions in the pathophysiology of these disorders may be related to a cytoskeleton stress. However, recently Cofilin-1 has also been related to other biological processes such as cell death by apoptosis. In both cases, ATP depletion associated with the presence of reactive species and other stressors regulate Cofilin-1 by inducing the formation of aggregates composed primarily by actin and Cofilin-1, known as Cofilin/actin rods. These structures seem to be formed initially as a neuroprotective response to mitochondrial damage; but once the stressor persists they are thought to act as inducers of further impairments and loss of neuronal functions. Therefore, here we provide a brief overview of the current knowledge about the central role of Cofilin/actin rods formation, where its dysregulation and malfunction might be the trigger to neurodegeneration.
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high Cofilin 1 levels correlate with cisplatin resistance in lung adenocarcinomas
Tumor Biology, 2014Co-Authors: Matheus Becker, Marco Antonio De Bastiani, Carolina Beatriz Muller, Melissa Medeiros Markoski, Mauro A A Castro, Fabio KlamtAbstract:High Cofilin-1 levels have been shown to be an accurate prognostic biomarker in non-small cell lung cancer (NSCLC) and a predictive factor in drug resistance. Herein we explore the role of Cofilin-1 in cis-diamminedichloroplatinum(II) (cisplatin) resistance. We evaluated Cofilin-1 levels in intrinsically cisplatin-resistant A549 (ICR-A549) cells and determined the cisplatin toxicity in A549 cells transiently transfected and overexpressing CFL1 plasmid. Moreover, expression levels (activity) of the CFL1 gene network were analyzed in a cisplatin-resistant human lung adenocarcinoma cell panel. ICR-A549 cells, selected by challenging parental cells with 10-fold drug GI50 value, presented a sixfold increase in cisplatin GI50 value and an increased Cofilin-1 immunocontent (P < 0.01). In addition, cells transfected with Cofilin-1 became more resistant to cisplatin (P < 0.01). High activity of the CFL1 gene network was found in a cisplatin-resistant adenocarcinoma cell panel (P < 0.01). In vitro evidences suggest that Cofilin-1 is a biological predictor of cisplatin resistance, supporting new treatment initiatives based on Cofilin-1 levels to guide chemotherapeutic interventions in NSCLC patients.