DEPDC1B promotes migration and invasion in pancreatic ductal adenocarcinoma by activating the Akt/GSK3&amp;beta;/Snail pathway

Liu, Xu; Li, Tong; Huang, Xinyang; Wu, Wei; Li, Juanjuan; Wei, Leizhen; Qian, Yuting; Xu, Hui; Wang, Qi; Wang, Lifu

doi:10.3892/ol.2020.12009

Cited by 12 publications

(15 citation statements)

References 44 publications

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“…To evaluate the role of DEPDC1B in LIHC, we used various online tools to observe the expression of DEPDC1B in LIHC. As indicated in Figure 1 , the expression of DEPDC1B was higher in LIHC tissues than in normal tissues, and this is consistent with the results in non-small cell lung cancer, oral cancer, malignant melanoma ( Xu et al, 2019 ), bladder cancer ( Lai et al, 2020 ), glioblastoma, and pancreatic cancer ( Liu et al, 2020 ). Using qPCR assay, we confirmed the higher DEPDC1B mRNA expression levels in LIHC than that in the normal tissues ( Figure 7 ).…”

Section: Discussionsupporting

confidence: 88%

“…As a protein accumulating during G2 phase, Marchesi et al have reported that the role of DEPDC1B in coordinating de-adhesion and cell-cycle progression at mitotic entry ( Marchesi et al, 2014 ). Furthermore, increasing evidence in recent years suggests that the overexpression of DEPDC1B is associated with tumor aggressiveness and poor prognosis in cancers, such as oral cancer ( Su et al, 2014 ), malignant melanoma ( Xu et al, 2019 ), glioblastoma ( Chen et al, 2020 ), non-small cell lung ( Yang et al, 2014 ), and pancreatic cancers ( Mishra et al, 2019 ; Liu et al, 2020 ). These findings strongly suggest that DEPDC1B could potentially contribute to tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

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Identification and Validation of DEPDC1B as an Independent Early Diagnostic and Prognostic Biomarker in Liver Hepatocellular Carcinoma

et al. 2022

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Liver hepatocellular carcinoma (LIHC) is one of the most lethal tumors worldwide, and while its detailed mechanism of occurrence remains unclear, an early diagnosis of LIHC could significantly improve the 5-years survival of LIHC patients. It is therefore imperative to explore novel molecular markers for the early diagnosis and to develop efficient therapies for LIHC patients. Currently, DEPDC1B has been reported to participate in the regulation of cell mitosis, transcription, and tumorigenesis. To explore the valuable diagnostic and prognostic markers for LIHC and further elucidate the mechanisms underlying DEPDC1B-related LIHC, numerous databases, such as Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) were employed to determine the association between the expression of DEPDC1B and prognosis in LIHC patients. Generally, the DEPDC1B mRNA level was highly expressed in LIHC tissues, compared with that in normal tissues (p < 0.01). High DEPDC1B expression was associated with poor overall survival (OS) in LIHC patients, especially in stage II, IV, and grade I, II, III patients (all p < 0.05). The univariate and multivariate Cox regression analysis showed that DEPDC1B was an independent risk factor for OS among LIHC patients (HR = 1.3, 95% CI: 1.08–1.6, p = 0.007). In addition, the protein expression of DEPDC1B was validated using Human Protein Atlas database. Furthermore, the expression of DEPDC1B was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) assay using five pairs of matched LIHC tissues and their adjacent noncancerous tissues. The KEGG pathway analysis indicated that high expression of DEPDC1B may be associated with several signaling pathways, such as MAPK signaling, the regulation of actin cytoskeleton, p53 signaling, and the Wnt signaling pathways. Furthermore, high DEPDC1B expression may be significantly associated with various cancers. Conclusively, DEPDC1B may be an independent risk factor for OS among LIHC cancer patients and may be used as an early diagnostic marker in patients with LIHC.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Identification and Validation of DEPDC1B as an Independent Early Diagnostic and Prognostic Biomarker in Liver Hepatocellular Carcinoma

et al. 2022

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“…Our TCGA analysis revealed that DEPDC1B mRNA level was elevated in cutaneous melanoma and was correlated with poor survival. Several previous studies demonstrated that DEPDC1B expression is abnormally upregulated in various cancer types, including pancreatic ductal adenocarcinoma, [ 16 ] bladder cancer, [ 17 ] prostate cancer, [ 15 ] hepatocellular cancer, [ 18 ] glioblastoma, [ 14 ] oral cancer, [ 11 ] and soft‐tissue sarcomas, [ 37 ] and is associated with poor prognosis, yet the mechanism underlying its dysregulation remains unclear. We found that DEPDC1B expression was positively regulated by an oncogenic driver SOX10, which is required for melanoma formation and progression.…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulation of DEPDC1B expression is frequently associated with oncogenesis and metastasis in different cancer types. [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ] For example, exogenous expression of DEPDC1B delays cell death and increases cell proliferation in breast cancer cells; [ 19 ] overexpression of DEPDC1B enhances migration and invasion of non‐small‐cell lung cancer cells through the activation of Wnt/ β ‐catenin signaling; [ 10 ] DEPDC1B promotes anchoring‐independent growth, migration, and invasion of oral cancer cells via the activation of Rac1‐ERK signaling axis; [ 11 ] it also regulates the migration and invasion of pancreatic cancer through the activation of the RAC1/PAK1‐LIMK1‐cofilin1 signaling pathway; [ 13 ] contributes to the migration and invasion of pancreatic ductal adenocarcinoma cells via the activation of Akt/GSK3 β /Snail pathway; [ 16 ] and is required for the development of glioblastoma [ 14 ] and bladder cancer. [ 17 ] Recent studies have shown that DEPDC1B also induces epithelial‐mesenchymal transition and promotes prostate cancer cell proliferation via Rac1‐PAK signaling.…”

Section: Introductionmentioning

confidence: 99%

DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3

Fong

Liu

et al. 2022

Advanced Science

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The ability of melanoma to acquire metastasis through the induction of angiogenesis is one of the major causes of skin cancer death. Here, it is found that high transcript levels of DEP domain containing 1B (DEPDC1B) in cutaneous melanomas are significantly associated with a poor prognosis. Tissue microarray analysis indicates that DEPDC1B expression is positively correlated with SOX10 in the different stages of melanoma. Consistently, DEPDC1B is both required and sufficient for melanoma growth, metastasis, angiogenesis, and functions as a direct downstream target of SOX10 to partly mediate its oncogenic activity. In contrast to other tumor types, the DEPDC1B-mediated enhancement of melanoma metastatic potential is not dependent on the activities of RHO GTPase signaling and canonical Wnt signaling, but is acquired through secretion of signal peptide, CUB domain and EGF like domain containing 3 (SCUBE3), which is crucial for promoting angiogenesis in vitro and in vivo. Mechanistically, DEPDC1B regulates SCUBE3 protein stability through the competitive association with ubiquitin ligase cell division cycle 16 (CDC16) to prevent SCUBE3 from undergoing degradation via the ubiquitin-proteasome pathway. Importantly, expression of SOX10, DEPDC1B, and SCUBE3 are positively correlated with microvessel density in the advanced stage of melanomas. In conclusion, it is revealed that a SOX10-DEPDC1B-SCUBE3 regulatory axis promotes melanoma angiogenesis and metastasis, which suggests that targeting secreted SCUBE3 can be a therapeutic strategy against metastatic melanoma.

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“…Western blotting procedures were described in our previous study ( 18 ). The primary antibodies used were MISP (1:1,000, cat.no.…”

Section: Methodsmentioning

confidence: 99%

Up-Regulated MISP Is Associated With Poor Prognosis and Immune Infiltration in Pancreatic Ductal Adenocarcinoma

et al. 2022

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BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis. More effective biomarkers and treatment options remain to be discovered. Mitotic Spindle Positioning (MISP), also called C19orf21, has been reported to be upregulated in several malignancies. However, the effects of MISP on PDAC have yet to be investigated.Materials and MethodsThe differential expression of MISP at the mRNA and protein levels were evaluated using Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases, and was further verified by quantitative real-time PCR and western blotting in PDAC cell lines. Correlations between MISP expression and clinical characteristics were explored using Kaplan-Meier Plotter Database and clinical data from The Cancer Genome Atlas (TCGA). CCK-8 assays, Transwell assays, and immunoblotting were used to determine the role of MISP in PDAC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were executed by the R package ‘clusterProfiler’. Correlations between MISP expression and immune cell infiltration, immune checkpoints, immunophenoscore (IPS) and the tumor mutational burden (TMB) in PDAC were explored using the R package ‘CIBERSORT’, the Tumor Immune Estimation Resource 2.0 (TIMER2.0), and The Cancer Immunome Atlas (TCIA) database based on TCGA data.ResultMISP expression was significantly higher in pancreatic cancer tissues compared to normal pancreas tissues, which was associated with a poor prognosis. Increased expression of MISP was related to the proliferation, migration and invasion of PDAC cell lines. GO and KEGG pathway analyses determined that MISP is involved in the Ras signaling pathway and immune regulation. Higher expression of MISP was associated with decreased infiltration levels of activated CD4+ memory T cells, CD8+ T cells, M2 macrophages and neutrophils. Furthermore, increased MISP was associated with lower expression of immune checkpoint molecules, higher gene mutation burden and IPS.ConclusionsThis study reveals that MISP, which is associated with the progression and prognosis of PDAC, may exert a potential regulatory effect on immune infiltration and predict the response to immunotherapy in PDAC.

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DEPDC1B promotes migration and invasion in pancreatic ductal adenocarcinoma by activating the Akt/GSK3β/Snail pathway

Cited by 12 publications

References 44 publications

Identification and Validation of DEPDC1B as an Independent Early Diagnostic and Prognostic Biomarker in Liver Hepatocellular Carcinoma

Identification and Validation of DEPDC1B as an Independent Early Diagnostic and Prognostic Biomarker in Liver Hepatocellular Carcinoma

DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3

Up-Regulated MISP Is Associated With Poor Prognosis and Immune Infiltration in Pancreatic Ductal Adenocarcinoma

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