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pmid:32266108

LPPR4 promotes peritoneal metastasis via Sp1/integrin α/FAK signaling in gastric cancer.

Dan Zang · Chuang Zhang · Ce Li · Yibo Fan · Zhi Li · Kezuo Hou · Xiaofang Che · Yunpeng Liu · Xiujuan Qu

American journal of cancer research · 2020

Paper

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Experiment

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Data

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Analysis

partial

Execution

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LPPR4 promotes peritoneal metastasis via Sp1/integrin α/FAK signaling in gastric cancer.
doi
null
pmid
32266108
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[0]
Dan Zang
[1]
Chuang Zhang
[2]
Ce Li
[3]
Yibo Fan
[4]
Zhi Li
[5]
Kezuo Hou
[6]
Xiaofang Che
[7]
Yunpeng Liu
[8]
Xiujuan Qu
journal
American journal of cancer research
year
2020
abstract
Gastric cancer (GC) is one of the most common malignancies which has high incidence and mortality worldwide. Peritoneal dissemination is the main route of metastasis in advanced GC. However, few reliable diagnostic or prognostic biomarkers are available for peritoneal metastasis of GC. This study aimed to investigate the effect of lipid phosphate phosphatase-related protein type 4 (LPPR4) on the prognosis of peritoneal metastasis in GC, so as to explore the underlying molecular mechanisms and clinical significance of the process. Differentially expressed genes (DEGs) between tumor tissues and adjacent normal tissues were identified. The prognostic values of the DEGs were tested in two independent cohorts (TCGA-STAD cohort and GSE62254 cohort). Eight DEGs including LPPR4 with prognostic value in GC peritoneal metastasis were identified. The expression of LPPR4 increased in peritoneal metastasis of GC tissues, and high LPPR4 expression was associated with poor overall survival in GC. Loss- and gain-of functional experiments were performed to reveal that LPPR4 could promote the migration, invasion and adhesion abilities of GC cells in vitro. Tumor peritoneal dissemination was investigated in a mouse model to reveal that LPPR4 could promote peritoneal metastasis of GC cells in vivo. According to the Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene set enrichment analysis (GSEA), LPPR4 was found to be related to focal adhesion, cell adhesion molecules (CAMs) and ECM-receptor interaction pathways. LPPR4 knockdown significantly inhibited the expression of integrin α1, integrin α2, integrin α5, integrin α6, integrin α7, p-FAK, p-Akt, p-Src and MMP2. Moreover, this process was regulated by the Specificity Protein 1 (Sp1) transcription factor. Taken together, LPPR4 plays an essential role in promoting peritoneal metastasis of GC through Sp1/integrin α/FAK signaling, and acts as a novel biomarker of prognosis of GC peritoneal metastasis. The results suggest that LPPR4 may serve as a new therapeutic target for patients with GC peritoneal metastasis.
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doi
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ritoneal dissemination was investigated in a mouse model to reveal that LPPR4 could promote peritonea
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ld promote peritoneal metastasis of GC cells in vivo. According to the Kyoto Encyclopedia of Gene
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ritoneal dissemination was investigated in a mouse model to reveal that LPPR4 could promote per
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and ECM-receptor interaction pathways. LPPR4 knockdown significantly inhibited the expression of in
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Complete file
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However, few reliable diagnostic or prognostic biomarkers are available for peritoneal metastasis of GC. This study aimed to investigate the effect of lipid phosphate phosphatase-related protein type 4 (LPPR4) on the prognosis of peritoneal metastasis in GC, so as to explore the underlying molecular mechanisms and clinical significance of the process. Differentially expressed genes (DEGs) between tumor tissues and adjacent normal tissues were identified. The prognostic values of the DEGs were tested in two independent cohorts (TCGA-STAD cohort and GSE62254 cohort). Eight DEGs including LPPR4 with prognostic value in GC peritoneal metastasis were identified. The expression of LPPR4 increased in peritoneal metastasis of GC tissues, and high LPPR4 expression was associated with poor overall survival in GC. Loss- and gain-of functional experiments were performed to reveal that LPPR4 could promote the migration, invasion and adhesion abilities of GC cells in vitro. Tumor peritoneal dissemination was investigated in a mouse model to reveal that LPPR4 could promote peritoneal metastasis of GC cells in vivo. According to the Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene set enrichment analysis (GSEA), LPPR4 was found to be related to focal adhesion, cell adhesion molecules (CAMs) and ECM-receptor interaction pathways. LPPR4 knockdown significantly inhibited the expression of integrin α1, integrin α2, integrin α5, integrin α6, integrin α7, p-FAK, p-Akt, p-Src and MMP2. Moreover, this process was regulated by the Specificity Protein 1 (Sp1) transcription factor. Taken together, LPPR4 plays an essential role in promoting peritoneal metastasis of GC through Sp1/integrin α/FAK signaling, and acts as a novel biomarker of prognosis of GC peritoneal metastasis. 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