High expression of ladinin-1 (LAD1) predicts adverse outcomes: a new candidate docetaxel resistance gene for prostatic cancer (PCa)

Li, Jianping; Wang, Ziming; Chong, Tie

doi:10.1080/21655979.2021.1968647

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…A physical interaction between LAD1 and Stratifin (14-3-3σ) has been reported to promote breast tumor invasion by regulating actin filament turnover ( 55 ). LAD1 is highly expressed in docetaxel-resistant prostate cancer cells but its expression is significantly suppressed in tumor samples after docetaxel treatment, suggesting that the upregulation of LAD1 may contribute to the development of docetaxel resistance in prostate cancer ( 56 ). WASF3 is a member of the Wiskott-Aldrich syndrome protein family and plays an important role in the regulation of actin cytoskeletal dynamics as well as in cancer cell invasion and metastasis ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes

Sun¹,

Zhang²,

Chu³

et al. 2023

J Gastrointest Oncol

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Background The incidence and mortality of pancreatic cancer are almost the same, and the 5-year survival rate is less than 10%. The high mortality of pancreatic cancer is related to chemo-radiotherapy. The present study aimed to establish a prognostic signature of pancreatic cancer based on chemo-radiotherapy resistant-related genes (CRRGs). Methods In this study, we explored the radiation-resistant and chemotherapy-resistant pancreatic cancer cell lines by colony formation and a subcutaneous tumor model in nude mice. Next, we obtained CRRGs from radiation- and gemcitabine-resistant pancreatic cancer cell lines in the Gene Expression Omnibus (GEO) database. Based on univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, a prognostic model of the pancreatic adenocarcinoma (PAAD) cohort in The Cancer Genome Atlas (TCGA) database (N=177) was established and verified using the GEO cohort data set (N=112). Finally, the functions of candidate target genes were verified by a methyl thiazolyl tetrazolium (MTT) assay, a colony formation assay, and a subcutaneous tumor model in nude mice. Results Through the in vitro and in vivo experiments, we found that radiotherapy- and chemotherapy-resistant pancreatic cancer cells were cross-resistant to chemotherapy and radiotherapy. We constructed a risk model consisting of nine CRRGs ( SNAP25 , GPR87 , DLL1 , LAD1 , WASF3 , ARHGAP29 , ZBED2 , GAD1 , and JAG1 ) by using public databases. According to the Kaplan-Meier curve analysis, the survival of the high-risk group was worse than that of the low-risk group. We then used nomograms to predict the 1/3/5-year overall survival (OS) in pancreatic cancer patients. We chose JAG1 as a candidate target since it has been proven to be involved in the stemness maintenance of cancer cells, and found that JAG1 silencing inhibited the proliferation and chemo-radiotherapy tolerance of pancreatic cancer cells. Conclusions This study established and validated a prognostic signature of pancreatic cancer using nine CRRGs. The in vitro and in vivo experiments showed that JAG1 could promote the proliferation and chemoradiotherapy tolerance of pancreatic cancer cell lines. These findings may offer new insights into the role of CRRGs in pancreatic cancer and provide novel prognostic biomarkers for the treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes

Sun¹,

Zhang²,

Chu³

et al. 2023

J Gastrointest Oncol

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“…Targeted therapy has become a promising treatment strategy for PC patients (Wang et al 2021a , b , c ). For example, ladinin-1 (LAD1) may serve as a potential prognostic factor in PC patients (Li et al 2021 ). BMH-21 was considered as a new potential molecule for treatment-resistant prostate cancer (Low et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

CACYBP knockdown inhibits progression of prostate cancer via p53

Liu

et al. 2022

J Cancer Res Clin Oncol

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Purpose Prostate cancer (PC) is one of the most common malignant tumors of genitourinary system in men. CACYCLIN binding protein (CACYBP) is involved in the progression of a variety of cancers. The aim of this study was to explore the expression and functional role of CACYBP in PC. Methods The expression of CACYBP in PC was evaluated by immunohistochemical (IHC) staining and qRT-PCR. Subsequently, we established lentivirus-mediated CACYBP knockdown in PC cell lines. The biological roles of CACYBP on proliferation, apoptosis, cycle distribution, migration and tumor formation of PC were investigated by Celigo cell counting assay, flow cytometry, transwell assay, wound-healing assay and mice xenograft models, respectively. Results CACYBP was highly expressed in PC and was positively correlated with the pathological grade of PC patients. Knockdown of CACYBP inhibited proliferation, enhanced apoptosis, arrested cell cycle in G2 and suppressed migration of PC cell lines in vitro. In addition, CACYBP knockdown weakened the tumor growth of PC in vivo. Moreover, addition of p53 inhibitor could effectively alleviate the inhibitory effect of CACYBP knockdown on cell activity. Conclusion This study revealed that knockdown of CACYBP inhibited the proliferation, migration and tumorigenicity of PC, which may serve as a potential therapeutic target for the treatment of PC.

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“…It may contribute to the stability of the association of the epithelial layers with the underlying mesenchyme. At present, some articles have shown that LAD1 is expressed in some cancers, such as colorectal cancer [ 14 ], prostatic cancer [ 15 ], laryngeal cancer [ 16 ], and breast cancer [ 17 ], demonstrating that LAD1 expression is related to cancer migration and invasion. An analysis of METABRIC, a large clinical dataset of approximately 2000 breast cancer patients, demonstrates that a high abundance of the LAD1 transcript is associated with poor prognosis in breast cancer patients [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Tumorigenic Effect of the High Expression of Ladinin-1 in Lung Adenocarcinoma and Its Potential as a Therapeutic Target

Liu

et al. 2023

Molecules

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The oncogenic role of Ladinin-1 (LAD1), an anchoring filament protein, is largely unknown. In this study, we conducted a series of studies on the oncogenic role of LAD1 in lung adenocarcinoma (LUAD). Firstly, we analyzed the aberrant expression of LAD1 in LUAD and its correlation with patient survival, tumor immune infiltration, and the activation of cancer signaling pathways. Furthermore, the relationship between LAD1 expression and K-Ras and EGF signaling activation, tumor cell proliferation, migration, and colony formation was studied by gene knockout/knockout methods. We found that LAD1 was frequently overexpressed in LUAD, and high LAD1 expression predicts a poor prognosis. LAD1 exhibits promoter hypomethylation in LUAD, which may contribute to its mRNA upregulation. Single-sample gene set enrichment analysis (ssGSEA) showed that acquired immunity was negatively correlated with LAD1 expression, which was verified by the downregulated GO terms of “Immunoglobulin receptor binding” and “Immunoglobulin complex circulating” in the LAD1 high-expression group through Gene Set Variation Analysis (GSVA). Notably, the Ras-dependent signature was the most activated signaling in the LAD1 high-expression group, and the phosphorylation of downstream effectors, such as ERK and c-jun, was strongly inhibited by LAD1 deficiency. Moreover, we demonstrated that LAD1 depletion significantly inhibited the proliferation, migration, and cell-cycle progression of LUAD cells and promoted sensitivity to Gefitinib, K-Ras inhibitor, and paclitaxel treatments. We also confirmed that LAD1 deficiency remarkably retarded tumor growth in the xenograft model. Conclusively, LAD1 is a critical prognostic biomarker for LUAD and has potential as an intervention target.

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High expression of ladinin-1 (LAD1) predicts adverse outcomes: a new candidate docetaxel resistance gene for prostatic cancer (PCa)

Cited by 10 publications

References 48 publications

Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes

Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes

CACYBP knockdown inhibits progression of prostate cancer via p53

The Tumorigenic Effect of the High Expression of Ladinin-1 in Lung Adenocarcinoma and Its Potential as a Therapeutic Target

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