ASAP1 promotes tumor progression and angiogenesis and independently predicts poor prognosis and lymph node metastasis of gastric cancer

Abstract Background: Although ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1(ASAP1) is involved in the development of various malignancies, its clinical significance and mechanism in gastric cancer (GC) remains unclear.Methods: The effects of ASAP1 on tumor progression, angiogenesis, and epithelial-mesenchymal transition were evaluated in vitro. The effects of ASAP1 on tumor growth and angiogenesis were also explored in vivo. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to gather ASAP1 expression data.Results: It showed that ASAP1 expression strongly correlated with the TNM stage (P < 0.0001) and lymph node metastasis (P < 0.0001). Multivariate analyses indicated that ASAP1 overexpression (P < 0.0001) was an independent predictor for overall survival in patients with GC. Moreover, the results revealed that ASAP1 overexpression was independently related to lymph node metastasis (P = 0.0001). ASAP1 knockdown inhibited tumor cell motility, migration, invasion, and angiogenesis, which was accompanied with the downregulation of metastatic and angiogenic biomarkers. Furthermore, ASAP1 inhibition resulted in the simultaneous downregulation of mesenchymal markers and upregulation of epithelial markers. In addition, ASAP1 promoted tumor growth and angiogenesis in the xenograft mice model. The combined datasets (TCGA and GEO) suggested that ASAP1 was associated with malignant behavior of tumor and tumor invasion, metastasis, and angiogenesis.Conclusion: To our knowledge, our study is the first to reveal that ASAP1 promotes tumor progression and angiogenesis, and indicates a prognostic potential in GCs.

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Association of HIF-1α and NDRG2 expression with EMT in gastric cancer tissues

Open Life Sciences ◽

10.1515/biol-2019-0025 ◽

2019 ◽

Vol 14 (1) ◽

pp. 217-223

Author(s):

Ren-Xiang Wang ◽

Xia-Wan Ou ◽

Ma-Fei Kang ◽

Zu-Ping Zhou

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Epithelial Mesenchymal Transition ◽

Hypoxia Inducible Factor ◽

Mesenchymal Transition ◽

Node Metastasis ◽

Significant Difference ◽

Cancer Tissues ◽

E Cadherin

AbstractObjectiveThis study aims to investigate the differences in the expression of hypoxia-inducible factor-1α (HIF-1α), N-myc downstream-regulated gene 2 (NDRG2) and epithelial mesenchymal transition (EMT)-related proteins in normal gastric tissues, gastric cancer tissues and lymph node metastasis.MethodsImmunohistochemistry was used to detect the expression of HIF-1α, NDRG2, E-cadherin, Snail and Twist in normal gastric tissues, gastric cancer tissues and lymph node metastasis.ResultsIn normal gastric tissues, HIF-1α was not expressed, NDRG2 was highly expressed. There was a significant between the expression of NDRG2 and Snail, as well as of NDRG2 and Twist. In gastric cancer tissues, there was no statistically difference between the expression of HIF-1α and E-cadherin, NDRG2 and E-cadherin. However, there was a significant difference in expression between the expression of HIF-1α and Snail, HIF-1α and Twist, NDRG2 and Snail, and NDRG2 and Twist. In lymph node metastasis tissues, we show that HIF-1α was highly expressed, while NDRG2 was not, and the difference between the expression of HIF-1α and E-cadherin, HIF-1α and Snail, HIF-1α and Twist was not significant.ConclusionHIF-1α may promote EMT, possibly by inhibiting the expression of NDRG2.

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Predictive value for lymph node metastasis of epithelial-mesenchymal transition and cancer stem cell marker expression in early gastric cancer

Pathology - Research and Practice ◽

10.1016/j.prp.2017.03.010 ◽

2017 ◽

Vol 213 (9) ◽

pp. 1221-1226

Author(s):

Kyung Han Nam ◽

Hyuk Yoon ◽

Kyungbun Lee ◽

Do Joong Park ◽

Hyung-Ho Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cell ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Epithelial Mesenchymal Transition ◽

Stem Cell Marker ◽

Cancer Stem Cell Marker ◽

Cell Marker ◽

Mesenchymal Transition ◽

Node Metastasis

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microRNA-33a prevents epithelial-mesenchymal transition, invasion, and metastasis of gastric cancer cells through the Snail/Slug pathway

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00284.2018 ◽

2019 ◽

Vol 317 (2) ◽

pp. G147-G160 ◽

Cited By ~ 4

Author(s):

Di-Di Chen ◽

Jiang-Ting Cheng ◽

Arvine Chandoo ◽

Xiang-Wei Sun ◽

Liang Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Normal Tissues ◽

Node Metastasis

Invasion and metastasis are responsible for the majority of deaths in gastric cancer (GC). microRNA-33a (miR-33a) might function as a tumor suppressor in multiple cancers. Here, we describe the regulation and function of miR-33a in GC and mechanisms involved in epithelial-mesenchymal transition (EMT) and metastasis. First, GC tissues and adjacent normal tissues were collected. miR-33a upregulation or SNAI2 depletion on GC cells were introduced to assess the detailed regulatory mechanism of them. We assessed the expression of miR-33a, SNAI2, Snail/Slug signaling pathway-related genes, and EMT-related markers in GC tissues and cells. miR-33a distribution in GC tissues and adjacent normal tissues was measured. Cell proliferation, migration and invasion, and cell cycle distribution were assessed. In nude mice, GC tumor growth and lymph node metastasis were observed. Furthermore, the predicative value of miR-33a in the prognosis of GC patients was evaluated. The obtained results indicated that lowly expressed miR-33a, highly expressed SNAI2, activated Snail/Slug, and increased EMT were identified in GC tissues. miR-33a was located mainly in the cytoplasm. miR-33a targeted and negatively regulated SNAI2. MKN-45 and MKN-28 cell lines were selected for in vitro experiments. Upregulated miR-33a expression or siRNA-mediated silencing of SNAI2 suppressed the activation of Snail/Slug, whereby GC cell proliferation, invasion and migration, EMT, tumor growth, and lymph node metastasis were inhibited. High expression of miR-33a was a protective factor influencing the prognosis of GC. This study suggests that miR-33a inhibited EMT, invasion, and metastasis of GC through the Snail/Slug signaling pathway by modulating SNAI2 expression. NEW & NOTEWORTHY miR-33a targets and inhibits the expression of SNAI2, overexpression of SNAI2 activates the Snail/Slug signaling pathway, the Snail/Slug signaling pathway promotes GC cell proliferation, invasion, and metastasis, and overexpression of miR-33a inhibits cell proliferation, invasion, and metastasis. This study provides a new therapeutic target for the treatment of GC.

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