CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

AbstractThe chemokine receptor CXCR7 has been suggested to play important roles in the progression of several types of cancers. However, few studies have investigated the biological roles of CXCR7 in head and neck squamous cell carcinoma (HNSCC). CXCR7 expression and its clinical implications were examined in 103 HNSCC tissues using immunohistochemistry (IHC). The biological roles and mechanisms of CXCR7-mediated signaling pathways were investigated in HNSCC cells through CXCR7 overexpression in vitro and in vivo. High expression of CXCR7 was significantly associated with tumor size (P = 0.007), lymph node metastasis (P = 0.004), and stage (P = 0.020) in HNSCC. Overexpression of CXCR7 in HNSCC cells enhanced cell migration and invasion in vitro and promoted lymph node metastasis in vivo. CXCR7 also induced epithelial–mesenchymal transition through PI3K/AKT. CXCR7 increased secretion of transforming growth factor-β1 (TGF-β1) and promoted EMT through phosphorylated Smad2/3. Taken together, our results provide functional and mechanistic roles of CXCR7 as a master regulator of oncogenic TGF-β1/Smad2/3 signaling in HNSCC, suggesting that CXCR7 might be a therapeutic target for the treatment of HNSCC.

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Serum exosomal miR-4787-3p as potential lymph node metastasis and prognostic marker in esophageal squamous cell carcinoma.

10.21203/rs.3.rs-317660/v1 ◽

2021 ◽

Author(s):

Shuang Liu ◽

Zheng Lin ◽

Jianwen Wang ◽

Zerong Zheng ◽

Wenqing Rao ◽

...

Keyword(s):

Regression Analysis ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cox Regression ◽

High Serum ◽

Migration And Invasion ◽

Cox Regression Analysis ◽

Mirna Array ◽

Node Metastasis

Abstract Background: To explore the miR-4787-3p expression levels in the serum exosome and tissue and its role in lymph node metastasis and prognosis in ESCC. Methods: The miRNA array was conducted to detect the ESCC serum exosomal miRNAs expression. A receiver operating characteristic (ROC) curve was constructed to determine the predictive ESCC with lymph node metastasis efficacy of serum exosomal miR-4784-3p. The Cox regression analysis was preformed to explore prognostic factors for ESCC. Transwell assay and CCK-8 assays were utilized to evaluate cell migration, invasion, and proliferation, respectively. Results: High serum exosomal miR-4787-3p expression was demonstrated in lymph node metastasis group (P =0.011). The serum exosomal miR-4787-3p expression was significantly associated with histologic grade (P = 0.010), and TNM stage (P = 0.033). However, there was no significant relationship between tissue miR-4787-3p expression and clinical characteristics (P >0.05). ROC analyses revealed that the AUCs of serum exosomal miR-4787-3p for lymph node metastasis prediction was 0.787. The Cox regression analysis found that high expression serum exosomal miR-4787-3p were correlated with poor prognoses (for OS, HR=2.68, 95% CI: 1.02~7.04; for DFS, HR = 2.65, 95% CI: 1.05~6.68). Nevertheless, no association between tissue miR-4787-3p expression and ESCC prognosis. In addition, upregulated expression of miR-4787-3p could promote migration and invasion in vitro. Conclusions: Serum exosomal miR-4787-3p can be promising biomarkers for ESCC metastasis and prognosis

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Cir-ITCH inhibits gastric cancer migration, invasion and proliferation by regulating the Wnt/β-catenin pathway

Scientific Reports ◽

10.1038/s41598-020-74452-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yang Peng ◽

Hong Hong Wang

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cancer Prognosis ◽

Luciferase Reporter ◽

Circular Rnas ◽

Node Metastasis ◽

Cancer Tissues

Abstract Circular RNAs (circRNAs) are differentially expressed in various tumours, but the expression and regulatory mechanisms of circular RNA ITCH (cir-ITCH) in gastric cancer remain unclear. For this reason, in the present study, we assessed the expression of cir-ITCH and the associated regulatory mechanism of cir-ITCH in gastric cancer. Through RTq-PCR assays, we observed that cir-ITCH expression was attenuated in gastric cancer cell lines and tissues, with cir-ITCH expression in gastric cancer tissues with lymph node metastasis being considerably lower than that observed in gastric cancer tissues without lymph node metastasis. In addition, we demonstrated that cir-ITCH or linear ITCH may be a useful marker for gastric cancer prognosis by Kaplan–Meier survival analysis. We also showed that cir-ITCH overexpression could increase linear ITCH expression through miR-17 via RNA immunoprecipitation (RIP) and luciferase reporter assays. Moreover, in vivo and in vitro experimental results showed that cir-ITCH can act as a tumour suppressor to prevent gastric cancer tumourgenesis by sponging miR-17. The Wnt/β-catenin pathway plays a crucial role during the carcinogenesis of cancers, and we observed that cir-ITCH could negatively regulate Wnt/β-catenin signalling, which could be restored by miR-17. In summary, cir-ITCH was shown to prevent gastric cancer tumourgenesis through the Wnt/β-catenin signalling pathway by sequestering miR-17.

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TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin

BMC Cancer ◽

10.1186/s12885-019-6453-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Yanan Jiang ◽

Jing Zhang ◽

Jimin Zhao ◽

Zhenzhen Li ◽

Hanyong Chen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Protein Kinase ◽

Lymph Node Metastasis ◽

Esophageal Squamous Cell Carcinoma ◽

Erk Signaling ◽

Node Metastasis

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is distal metastasis. A comprehensive understanding of the molecular mechanism underlying metastasis is needed for improving patient prognosis. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase, which plays a vital role in various physiological and pathophysiological processes. However, the role of TOPK in ESCC metastasis is unclear. Methods Tissue array was used to evaluate the correlation between TOPK expression and ESCC lymph node metastasis. Wound healing assay, transwell assay, and lung metastasis mice model were used to examine the role of TOPK in the migration of ESCC cells in vitro and in vivo. Protein kinase array, mass spectrometry (MS), and molecular modeling were used to examine the pathways and direct target proteins of TOPK that are involved in ESCC metastasis. Additionally, immunofluorescence and western blotting analyses were performed to verify these findings. Results The enhanced expression of TOPK was correlated with lymph node metastasis in the ESCC tissues. TOPK knockdown or treatment with the TOPK inhibitor (HI-TOPK-032) decreased the invasion and migration of ESCC cells in vitro. HI-TOPK-032 also inhibited the lung metastasis in ESCC cell xenograft in vivo model. Moreover, TOPK promoted the invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin. Conclusion The findings of this study reveal that TOPK is involved in ESCC metastasis and promoted the ESCC cell mobility by activating the Src/GSK3β/STAT3 and ERK signaling pathways. This indicated that TOPK may be a potential molecular therapeutic target for ESCC metastasis.

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549 FIRST ESTABLISHMENT OF PAIRED PRIMARY TUMOUR AND LYMPH NODE METASTASIS CELL LINES FOR REPETITIVE IN-VIVO AND IN-VITRO INVESTIGATIONS IN PENILE SQUAMOUS CELL CARCINOMA

European Urology Supplements ◽

10.1016/s1569-9056(10)60540-4 ◽

2010 ◽

Vol 9 (2) ◽

pp. 187-188

Author(s):

C.M. Naumann ◽

H. Kalthoff ◽

I. Leuschner ◽

D. Emme ◽

L. Weder ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cell Carcinoma ◽

Cell Lines ◽

Primary Tumour ◽

Node Metastasis ◽

Penile Squamous Cell Carcinoma

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Effects of 6,8-Diprenylgenistein on VEGF-A-Induced Lymphangiogenesis and Lymph Node Metastasis in an Oral Cancer Sentinel Lymph Node Animal Model

International Journal of Molecular Sciences ◽

10.3390/ijms22020770 ◽

2021 ◽

Vol 22 (2) ◽

pp. 770

Author(s):

Mun Gyeong Bae ◽

Jeon Hwang-Bo ◽

Dae Young Lee ◽

Youn-Hyung Lee ◽

In Sik Chung

Keyword(s):

Animal Model ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Lymph Node Metastasis ◽

Oral Cancer ◽

Tube Formation ◽

Inhibitory Effects ◽

Node Metastasis

Background: The major determining factor of prognosis of oral squamous cell carcinoma is cervical lymph node metastasis. 6,8-Diprenylgenistein (6,8-DG), an isoflavonoid isolated from Cudrania tricuspidata has been reported to have anti-microbial and anti-obesity activities. However, its effects on lymphangiogenesis and lymph node metastasis in oral cancer have not yet been reported. Methods: To investigate the in vitro inhibitory effects of 6,8-DG on VEGF-A-induced lymphangiogenesis, we performed the proliferation, tube formation, and migration assay using human lymphatic microvascular endothelial cells (HLMECs). RT-PCR, Western blot, immunoprecipitation, ELISA and co-immunoprecipitation assays were used to investigate the expression levels of proteins, and mechanism of 6,8-DG. The in vivo inhibitory effects of 6,8-DG were investigated using an oral cancer sentinel lymph node (OCSLN) animal model. Results: 6,8-DG inhibited the proliferation, migration and tube formation of rhVEGF-A treated HLMECs. In addition, the in vivo lymphatic vessel formation stimulated by rhVEGF-A was significantly reduced by 6,8-DG. 6,8-DG inhibited the expression of VEGF-A rather than other lymphangiogenic factors in CoCl2-treated SCCVII cells. 6,8-DG inhibited the expression and activation of VEGFR-2 stimulated by rhVEGF-A in HLMECs. Also, 6,8-DG inhibited the activation of the lymphangiogenesis-related downstream signaling factors such as FAK, PI3K, AKT, p38, and ERK in rhVEGF-A-treated HLMECs. Additionally, 6,8-DG inhibited the expression of the hypoxia-inducible factor (HIF-1α), which is involved in the expression of VEGF-A in CoCl2-treated SCCVII cells, and 6,8-DG inhibited VEGF-A signaling via interruption of the binding of VEGF-A and VEGFR-2 in HLMECs. In the VEGF-A-induced OCSLN animal model, we confirmed that 6,8-DG suppressed tumor-induced lymphangiogenesis and SLN metastasis. Conclusion: These data suggest that 6,8-DG inhibits VEGF-A-induced lymphangiogenesis and lymph node metastasis in vitro and in vivo. Furthermore, the inhibitory effects of 6,8-DG are probably mediated by inhibition of VEGF-A expression in cancer cells and suppression of the VEGF-A/VEGFR-2 signaling pathway in HLMEC. Thus, 6,8-DG could be novel and valuable therapeutic agents for metastasis prevention and treatment of oral cancer.

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miR-339-5p inhibits cell migration and invasion in vitro and may be associated with the tumor-node-metastasis staging and lymph node metastasis of non-small cell lung cancer

Oncology Letters ◽

10.3892/ol.2014.2165 ◽

2014 ◽

Vol 8 (2) ◽

pp. 719-725 ◽

Cited By ~ 21

Author(s):

YUN LI ◽

WEIGUO ZHAO ◽

PENGTAO BAO ◽

CHUNSUN LI ◽

XIU QING MA ◽

...

Keyword(s):

Lung Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Small Cell ◽

Migration And Invasion ◽

Small Cell Lung ◽

Tumor Node Metastasis ◽

Node Metastasis ◽

Tumor Node Metastasis Staging

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TOPK Promotes Metastasis of Esophageal Squamous Cell Carcinoma by Activating the Src/GSK3β/STAT3 Signaling Pathway via γ-Catenin

10.21203/rs.2.13096/v3 ◽

2019 ◽

Author(s):

Yanan Jiang ◽

Jing Zhang ◽

Jimin Zhao ◽

Zhenzhen Li ◽

Hanyong Chen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Protein Kinase ◽

Lymph Node Metastasis ◽

Esophageal Squamous Cell Carcinoma ◽

Erk Signaling ◽

Node Metastasis

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is distal metastasis. A comprehensive understanding of the molecular mechanism underlying metastasis is needed for improving patient prognosis. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase, which plays a vital role in various physiological and pathophysiological processes. However, the role of TOPK in ESCC metastasis is unclear. Methods Tissue array was used to evaluate the correlation between TOPK expression and ESCC lymph node metastasis. Wound healing assay, transwell assay, and lung metastasis mice model were used to examine the role of TOPK in the migration of ESCC cells in vitro and in vivo. Protein kinase array, mass spectrometry (MS), and molecular modeling were used to examine the pathways and direct target proteins of TOPK that are involved in ESCC metastasis. Additionally, immunofluorescence and western blotting analyses were performed to verify these findings. Results The enhanced expression of TOPK was correlated with lymph node metastasis in the ESCC tissues. TOPK knockdown or treatment with the TOPK inhibitor (HI-TOPK-032) decreased the invasion and migration of ESCC cells in vitro. HI-TOPK-032 also inhibited the lung metastasis in ESCC cell xenograft in vivo model. Moreover, TOPK promoted the invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin. Conclusion The findings of this study reveal that TOPK is involved in ESCC metastasis and promoted the ESCC cell mobility by activating the Src/GSK3β/STAT3 and ERK signaling pathways. This indicated that TOPK may be a potential molecular therapeutic target for ESCC metastasis.

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