Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported t...Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.展开更多
A growing number of studies have demonstrated that the skeleton is an endocrine organ that is involved in glucose metabolism and plays a significant role in human glucose homeostasis.However,there is still a limited u...A growing number of studies have demonstrated that the skeleton is an endocrine organ that is involved in glucose metabolism and plays a significant role in human glucose homeostasis.However,there is still a limited understanding of the in vivo glucose uptake and distribution across the human skeleton.To address this issue,we aimed to elucidate the detailed profile of glucose uptake across the skeleton using a total-body positron emission tomography(PET)scanner.A total of 41 healthy participants were recruited.Two of them received a 1-hour dynamic total-body^(18)F-fluorodeoxyglucose(^(18)F-FDG)PET scan,and all of them received a10-minute static total-body^(18)F-FDG PET scan.The net influx rate(K_i)and standardized uptake value normalized by lean body mass(SUL)were calculated as indicators of glucose uptake from the dynamic and static PET data,respectively.The results showed that the vertebrae,hip bone and skull had relatively high Kiand SUL values compared with metabolic organs such as the liver.Both the K_(i) and SUL were higher in the epiphyseal,metaphyseal and cortical regions of long bones.Moreover,trends associated with age and overweight with glucose uptake(SUL_(max)and SUL_(mean))in bones were uncovered.Overall,these results indicate that the skeleton is a site with significant glucose uptake,and skeletal glucose uptake can be affected by age and dysregulated metabolism.展开更多
Myeloid sarcoma(MS)is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia(AML).This neoplasm can also be an initial manifestation of relapse in a previously treated A...Myeloid sarcoma(MS)is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia(AML).This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission.A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010.After one month,bone marrow biopsy and aspiration confirmed the diagnosis of AML.Allogeneic mobilization peripheral blood stem cell transplantation was performed,with the sister of the patient as donor,after complete remission(CR)was achieved by chemotherapy.Five months after treatment,an adrenal mass was detected by positron emission tomography-computed tomography(PET-CT).Radiotherapy was performed for the localized mass after a multidisciplinary team(MDT)discussion.The patient is still alive as of May 2013,with no evidence of recurrent MS or leukemia.展开更多
Objective:Androgen deprivation therapy(ADT)is still the principal treatment option for prostate cancer(PCa).In addition to reactivation of androgen receptor signaling,the resistance of PCa to apoptosis during ADT also...Objective:Androgen deprivation therapy(ADT)is still the principal treatment option for prostate cancer(PCa).In addition to reactivation of androgen receptor signaling,the resistance of PCa to apoptosis during ADT also contributes to castration resistant PCa(CRPC).A previous study reported that gene transfer of IL-13Rα2 into PCa cells sensitized the cells to the IL-13R-targeted cytotoxin IL13Rα1,leading to apoptosis.Compared with IL-13Rα2,IL13Rα1 is more constitutively expressed in PCa cells,but its function in PCa remains to be established.Methods:We determined the role and expression of IL13Rα1 in PCa cancer cells using western blotting,flow cytometry,and cell proliferation assays.Co-immunoprecipitation and mass spectrometry were used to identify the proteins that interacted with IL13Rα1,to elucidate its function.Results:In this study,we showed that IL13Rα1 was selectively suppressed in androgen-deprived PCa cells and that its suppression tended to be associated with poor prognoses of PCa patients.IL13Rα1 overexpression promoted apoptosis and inhibited tumor growth under androgen-deprived or castrated conditions(P<0.01).Mechanistically,IL13Rα1 recruited and facilitated ubiquitin protein ligase E3C-mediated ubiquitination and degradation of hexokinase 2(HK2),resulting in glycolytic inhibition and eventually leading to PCa cell apoptosis.Furthermore,our data revealed that mutated ataxia-telangiectasia kinase phosphorylated and facilitated the selective ubiquitin proteasome-mediated degradation of HK2.Notably,IL13Rα1-overexpressing PCa cells were more susceptible to apoptosis and exhibited reduced tumor growth after exposure to the HK2 inhibitor,2-deoxy-D-glucose(P<0.01).Conclusions:Our data identified a tumor suppressor role for IL13Rα1 in preventing the resistance of PCa cells to apoptosis during androgen deprivation by inhibiting glycolysis.IL13Rα1-mediated signaling involving HK2 may therefore provide a novel treatment target and strategy for CRPC.展开更多
Background:Brain metastases are frequent complications for lung cancer patients.However,changes in the brain of lung cancer patients have received little attention.We aimed to explore whether alterations in brain gluc...Background:Brain metastases are frequent complications for lung cancer patients.However,changes in the brain of lung cancer patients have received little attention.We aimed to explore whether alterations in brain glucose uptake and brain texture occur in non-small cell lung cancer(NSCLC)patients and to investigate associations between brain alterations and NSCLC via the uEXPLORER positron emission tomography/computed tomography(PET/CT)system.Methods:In total,105 participants were enrolled,including 55 healthy con-trols and 50 NSCLC patients.Images were acquired using the PET/CT system.Standardized uptake values normalized by lean body mass were calculated as indicators of glucose uptake.Correlation analysis was conducted between aberrant brain glucose uptake,glucose uptake of cancer lesions,and con-centrations of serum lung cancer markers.Radiomics was used to investigate whether features extracted from regions with altered brain glucose uptake could serve as biomarkers of lung cancer progression.Results:Compared with healthy controls,NSCLC patients showed decreased standardized uptake values normalized by lean body mass in the left insula,medial frontal gyrus,and anterior cingulate.Correlation analysis demon-strated that glucose uptake of the anterior cingulate was negatively correlated with serum lung cancer marker concentrations.Radiomic features on PET/CT images of the above brain regions could classify NSCLC patients and healthy controls with an accuracy of 79%.Conclusions:NSCLC patients exhibited altered brain glucose uptake and changes in brain textures.These alterations may reflect alterations in behav-ioral domains in NSCLC and may be related to altered lung-brain interactions and potential brain metastasis of NSCLC.展开更多
The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)...The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)offers complementary information from PET and MR in the diagnosis of obstructive jaundice and is becoming widely adopted in clinical setting.While preserving its diagnostic accuracy,it is important to standardize and streamline the clinical scan protocol of PET/MR in evaluating obstructive jaundice.Based on literature review and experience of large number of clinical cases from the author group,this article reports an expert consensus on imaging protocol optimization and case interpretation template standardization.展开更多
Tumor metastasis accounts for over 90%of tumor-related deaths,prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues.However,early det...Tumor metastasis accounts for over 90%of tumor-related deaths,prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues.However,early detection of metastasis lesions by tracking tumor markers alone has proven to be challenging.Herein,we reported a glycopeptide-based bispecific fluorescence probe(bsProbe)for earlier detection of bladder cancer and metastasis.By simultaneously recognition(tumor&tumor microenvironment)and in vivo self-assembly,the tumor accumulation of bsProbe(12.3%ID/g)was obviously increased by∼6 fold compared with that in CXCR4 specific fluorescence probe(sProbe),indicating the obvious advantages of bsProbe over existing tumor metastasis detection probes.Additionally,bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio(SNR:approximately 9.5),permitting early diagnosis of lung micro-metastasis(∼1 mm),precise identifying of tumor boundaries and micro-tumors in orthotopic tumor models.More importantly,bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48%and sensitivity of 92.22%in 195 clinical specimens of bladder cancer patients.Taken together,this novel synergetic targeting(CD206×CXCR4)strategy provides an attractive method for earlier detection of bladder cancer and metastasis,which might be further extended to the imaging-guided surgery of clinical invisible tumors.展开更多
Aim:Brain metastases(BM)in patients with lung cancer(LC)are linked to unfavorable outcomes.The eukaryotic translation elongation factor 1 alpha 2(EEF1A2)is notably overexpressed across various cancer types and plays a...Aim:Brain metastases(BM)in patients with lung cancer(LC)are linked to unfavorable outcomes.The eukaryotic translation elongation factor 1 alpha 2(EEF1A2)is notably overexpressed across various cancer types and plays a role in promoting tumor initiation and progression.This research aimed to clarify the function of EEF1A2 in the context of lung cancer brain metastasis(LCBM)and to explore the mechanisms underlying its effects.Methods:To identify genes with differential expression between LC and LCBM samples,transcriptomic microarray analyses were conducted,confirming that EEF1A2 expression is elevated in LCBM.EEF1A2 expression levels were validated in multiple LC cell lines.PC9 and SPCA1 cells were transfected with lentiviral vectors carrying siRNAs targeting EEF1A2 to assess its role both in vitro and in vivo.Tandem mass tag proteomics was employed to identify proteins regulated by EEF1A2.The expression of EEF1A2,BCL10,and phosphorylated NF-κB in tumor tissues from LC and LCBM patients was analyzed.Results:Compared to the LC samples,the LCBM samples exhibited significantly higher levels of EEF1A2 expression.EEF1A2 knockdown in PC9 and SPCA1 cells resulted in substantial reductions in cell proliferation,migration,and invasion.Proteomic profiling revealed that BCL10 protein levels were markedly reduced in EEF1A2-knockdown cells.Additionally,there was a decrease in phosphorylated NF-κB,EGFR,and mesenchymal markers(N-cadherin,Twist,Snail,Slug,and Cdc42),along with an increase in E-cadherin expression.In a mouse model,EEF1A2 knockdown in PC9 cells significantly inhibited brain metastasis.Furthermore,patient samples presented elevated levels of EEF1A2,BCL10,and phosphorylated NF-κB in LCBM tissues than in LC tissues.Conclusion:Our research revealed that EEF1A2 is upregulated in LCBM,and that its knockdown suppresses brain metastasis by decreasing BCL10 expression,inhibiting NF-κB signaling,and reducing epithelial-mesenchymal transition markers.These results suggest that targeting EEF1A2 may be a promising therapeutic approach for preventing and treating brain metastasis in lung cancer patients.展开更多
基金the grants from National Key Research and Development Program of China(2016YFA0101002)National Key R&D Program of China(2017YFC1309603)National Natural Science Foundation of China(Nos.81170736,81570715,81870579).
文摘Insulin resistance is an essential characteristic of type 2 diabetes mellitus(T2DM),which can be induced by glucotoxicity and adipose chronic inflammation.Mesenchymal stem cells(MSCs)and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities.Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs.But the role of exosomes derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)in insulin resistance of human adipocytes is unclear.In this study,exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes.Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay.The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting.The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells(hAMSCs).The results showed that hAMSCs had better adipogenic ability than hUC-MSCs.After induction of mature adipocytes by adipogenesis of hAMSC,the model of insulin-resistant adipocytes was successfully established by TNF-αand high glucose intervention.After exosome treatment,the insulin-stimulated glucose uptake was significantly increased.In addition,the effect of exosomes could be stabilized for at least 48 h.Furthermore,the level of leptin was significantly decreased,and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment.In conclusion,exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes,and the mechanism involves the regulation of adipokines.
基金supported by the Science and Technology Funding from Jinan (grant number:2020GXRC018)the Academic Promotion Program of Shandong First Medical University (grant number:2019QL009)the Taishan Scholars Program of Shandong Province (grant number:TS201712065)。
文摘A growing number of studies have demonstrated that the skeleton is an endocrine organ that is involved in glucose metabolism and plays a significant role in human glucose homeostasis.However,there is still a limited understanding of the in vivo glucose uptake and distribution across the human skeleton.To address this issue,we aimed to elucidate the detailed profile of glucose uptake across the skeleton using a total-body positron emission tomography(PET)scanner.A total of 41 healthy participants were recruited.Two of them received a 1-hour dynamic total-body^(18)F-fluorodeoxyglucose(^(18)F-FDG)PET scan,and all of them received a10-minute static total-body^(18)F-FDG PET scan.The net influx rate(K_i)and standardized uptake value normalized by lean body mass(SUL)were calculated as indicators of glucose uptake from the dynamic and static PET data,respectively.The results showed that the vertebrae,hip bone and skull had relatively high Kiand SUL values compared with metabolic organs such as the liver.Both the K_(i) and SUL were higher in the epiphyseal,metaphyseal and cortical regions of long bones.Moreover,trends associated with age and overweight with glucose uptake(SUL_(max)and SUL_(mean))in bones were uncovered.Overall,these results indicate that the skeleton is a site with significant glucose uptake,and skeletal glucose uptake can be affected by age and dysregulated metabolism.
文摘Myeloid sarcoma(MS)is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia(AML).This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission.A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010.After one month,bone marrow biopsy and aspiration confirmed the diagnosis of AML.Allogeneic mobilization peripheral blood stem cell transplantation was performed,with the sister of the patient as donor,after complete remission(CR)was achieved by chemotherapy.Five months after treatment,an adrenal mass was detected by positron emission tomography-computed tomography(PET-CT).Radiotherapy was performed for the localized mass after a multidisciplinary team(MDT)discussion.The patient is still alive as of May 2013,with no evidence of recurrent MS or leukemia.
基金supported by the National Natural Science Foundation of China(Grant Nos.81772760 and 82072850)the Natural Science Foundation of Shandong Province(Grant Nos.ZR2020YQ55 and ZR2020QH327),the Shandong Taishan Scholarship(Grant No.tsqn20161076)+1 种基金the Innovation Project of Shandong Academy of Medical Sciences(2020)the program for Outstanding PhD candidate of Shandong University(2020)and Academic promotion programme of Shandong First Medical University(LJ001).
文摘Objective:Androgen deprivation therapy(ADT)is still the principal treatment option for prostate cancer(PCa).In addition to reactivation of androgen receptor signaling,the resistance of PCa to apoptosis during ADT also contributes to castration resistant PCa(CRPC).A previous study reported that gene transfer of IL-13Rα2 into PCa cells sensitized the cells to the IL-13R-targeted cytotoxin IL13Rα1,leading to apoptosis.Compared with IL-13Rα2,IL13Rα1 is more constitutively expressed in PCa cells,but its function in PCa remains to be established.Methods:We determined the role and expression of IL13Rα1 in PCa cancer cells using western blotting,flow cytometry,and cell proliferation assays.Co-immunoprecipitation and mass spectrometry were used to identify the proteins that interacted with IL13Rα1,to elucidate its function.Results:In this study,we showed that IL13Rα1 was selectively suppressed in androgen-deprived PCa cells and that its suppression tended to be associated with poor prognoses of PCa patients.IL13Rα1 overexpression promoted apoptosis and inhibited tumor growth under androgen-deprived or castrated conditions(P<0.01).Mechanistically,IL13Rα1 recruited and facilitated ubiquitin protein ligase E3C-mediated ubiquitination and degradation of hexokinase 2(HK2),resulting in glycolytic inhibition and eventually leading to PCa cell apoptosis.Furthermore,our data revealed that mutated ataxia-telangiectasia kinase phosphorylated and facilitated the selective ubiquitin proteasome-mediated degradation of HK2.Notably,IL13Rα1-overexpressing PCa cells were more susceptible to apoptosis and exhibited reduced tumor growth after exposure to the HK2 inhibitor,2-deoxy-D-glucose(P<0.01).Conclusions:Our data identified a tumor suppressor role for IL13Rα1 in preventing the resistance of PCa cells to apoptosis during androgen deprivation by inhibiting glycolysis.IL13Rα1-mediated signaling involving HK2 may therefore provide a novel treatment target and strategy for CRPC.
基金Taishan Scholar Project of Shandong Province,Grant/Award Number:TS201712065Chinese Polar Environment Comprehensive Investigation and Assessment Programmes,Grant/Award Number:2021YFE0204600Science and Technology Development Plan of Shandong Province,Grant/Award。
文摘Background:Brain metastases are frequent complications for lung cancer patients.However,changes in the brain of lung cancer patients have received little attention.We aimed to explore whether alterations in brain glucose uptake and brain texture occur in non-small cell lung cancer(NSCLC)patients and to investigate associations between brain alterations and NSCLC via the uEXPLORER positron emission tomography/computed tomography(PET/CT)system.Methods:In total,105 participants were enrolled,including 55 healthy con-trols and 50 NSCLC patients.Images were acquired using the PET/CT system.Standardized uptake values normalized by lean body mass were calculated as indicators of glucose uptake.Correlation analysis was conducted between aberrant brain glucose uptake,glucose uptake of cancer lesions,and con-centrations of serum lung cancer markers.Radiomics was used to investigate whether features extracted from regions with altered brain glucose uptake could serve as biomarkers of lung cancer progression.Results:Compared with healthy controls,NSCLC patients showed decreased standardized uptake values normalized by lean body mass in the left insula,medial frontal gyrus,and anterior cingulate.Correlation analysis demon-strated that glucose uptake of the anterior cingulate was negatively correlated with serum lung cancer marker concentrations.Radiomic features on PET/CT images of the above brain regions could classify NSCLC patients and healthy controls with an accuracy of 79%.Conclusions:NSCLC patients exhibited altered brain glucose uptake and changes in brain textures.These alterations may reflect alterations in behav-ioral domains in NSCLC and may be related to altered lung-brain interactions and potential brain metastasis of NSCLC.
基金supported by grants from the Shanghai Municipal Key Clinical Specialty Project(SHSLCZDZK03401)Shanghai Science and Technology Project(19DZ1930700)+1 种基金the Shanghai Science and Technology Committee Program(20DZ2201800)the Three-year Action Plan of Clinical Skills and Innovation of Shanghai Hospital Development Center(SHDC2020CR3079B).
文摘The cause of obstructive jaundice is usually complex which renders its differential diagnosis and lesion localization challenging in clinical practice.Integrated Positron Emission tomography/Magnetic Resonance(PET/MR)offers complementary information from PET and MR in the diagnosis of obstructive jaundice and is becoming widely adopted in clinical setting.While preserving its diagnostic accuracy,it is important to standardize and streamline the clinical scan protocol of PET/MR in evaluating obstructive jaundice.Based on literature review and experience of large number of clinical cases from the author group,this article reports an expert consensus on imaging protocol optimization and case interpretation template standardization.
基金supported by the National Key R&D Program of China(2022YFA1205701 and 2020YFA0210800)the National Natural Science Foundation of China(52322308,51725302,52273126,11621505,and 82302266)+8 种基金Beijing Nova Program(20230484237)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB36000000)the Key Research and Development Program of Heilongjiang Province(2022zX06004)Hong Kong scholar project(Xj2024052)Harbin Medical University Cancer Hospital Haiyan Foundation(JYQ2024-03 and JZD2024-17)the Nn10 program of Harbin Medical University Cancer Hospital(Nn102024-01)the Climing program of Harbin Medical University Cancer Hospital(PDYS2024-03)China Postdoctoral Science Foundation(2024MD753933)Heilongjiang Postdoctoral Fund(LBH-Z23221).
文摘Tumor metastasis accounts for over 90%of tumor-related deaths,prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues.However,early detection of metastasis lesions by tracking tumor markers alone has proven to be challenging.Herein,we reported a glycopeptide-based bispecific fluorescence probe(bsProbe)for earlier detection of bladder cancer and metastasis.By simultaneously recognition(tumor&tumor microenvironment)and in vivo self-assembly,the tumor accumulation of bsProbe(12.3%ID/g)was obviously increased by∼6 fold compared with that in CXCR4 specific fluorescence probe(sProbe),indicating the obvious advantages of bsProbe over existing tumor metastasis detection probes.Additionally,bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio(SNR:approximately 9.5),permitting early diagnosis of lung micro-metastasis(∼1 mm),precise identifying of tumor boundaries and micro-tumors in orthotopic tumor models.More importantly,bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48%and sensitivity of 92.22%in 195 clinical specimens of bladder cancer patients.Taken together,this novel synergetic targeting(CD206×CXCR4)strategy provides an attractive method for earlier detection of bladder cancer and metastasis,which might be further extended to the imaging-guided surgery of clinical invisible tumors.
基金supported by the National Nature Science Foundation of China(NSFC,81960455,82060519,81760519 and 81960215)Yunnan Provincial Science and Technology Department,Kunming Medical University Joint Special Project for Applied Basic Research(202001AY070001-080)Yunnan Provincial Department of Education Scientific Research Fund Project(2019J1274).
文摘Aim:Brain metastases(BM)in patients with lung cancer(LC)are linked to unfavorable outcomes.The eukaryotic translation elongation factor 1 alpha 2(EEF1A2)is notably overexpressed across various cancer types and plays a role in promoting tumor initiation and progression.This research aimed to clarify the function of EEF1A2 in the context of lung cancer brain metastasis(LCBM)and to explore the mechanisms underlying its effects.Methods:To identify genes with differential expression between LC and LCBM samples,transcriptomic microarray analyses were conducted,confirming that EEF1A2 expression is elevated in LCBM.EEF1A2 expression levels were validated in multiple LC cell lines.PC9 and SPCA1 cells were transfected with lentiviral vectors carrying siRNAs targeting EEF1A2 to assess its role both in vitro and in vivo.Tandem mass tag proteomics was employed to identify proteins regulated by EEF1A2.The expression of EEF1A2,BCL10,and phosphorylated NF-κB in tumor tissues from LC and LCBM patients was analyzed.Results:Compared to the LC samples,the LCBM samples exhibited significantly higher levels of EEF1A2 expression.EEF1A2 knockdown in PC9 and SPCA1 cells resulted in substantial reductions in cell proliferation,migration,and invasion.Proteomic profiling revealed that BCL10 protein levels were markedly reduced in EEF1A2-knockdown cells.Additionally,there was a decrease in phosphorylated NF-κB,EGFR,and mesenchymal markers(N-cadherin,Twist,Snail,Slug,and Cdc42),along with an increase in E-cadherin expression.In a mouse model,EEF1A2 knockdown in PC9 cells significantly inhibited brain metastasis.Furthermore,patient samples presented elevated levels of EEF1A2,BCL10,and phosphorylated NF-κB in LCBM tissues than in LC tissues.Conclusion:Our research revealed that EEF1A2 is upregulated in LCBM,and that its knockdown suppresses brain metastasis by decreasing BCL10 expression,inhibiting NF-κB signaling,and reducing epithelial-mesenchymal transition markers.These results suggest that targeting EEF1A2 may be a promising therapeutic approach for preventing and treating brain metastasis in lung cancer patients.
