Netrin-1 promotes gastric cancer cell proliferation and invasion via the receptor neogenin through PI3K/AKT signaling pathway

Yin, Kai; Wang, Linjun; Zhang, Xuan; He, Zhongyuan; Xia, Yiwen; Xu, Jianghao; Wei, Song; Li, Bowen; Li, Zheng; Sun, Guangli; Li, Qing; Xu, Hao; Xu, Zekuan

doi:10.18632/oncotarget.17750

Cited by 43 publications

(35 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, NTN1 has been demonstrated to regulate cancer cell proliferation, migration, invasion and apoptosis (5,8,9,12,13). Our previous study revealed that NTN1 promoted GC cells growth via its receptor neogenin (14); however, the downstream signaling pathway remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

et al. 2018

Self Cite

View full text Add to dashboard Cite

Netrin‑1 (NTN1) has been demonstrated to promote tumorigenesis in multiple types of cancer; however, its role in the growth of gastric cancer (GC) cells has not been described in detail. In the present study, the data suggested that NTN1 knockdown significantly decreased the proliferation of GC cells, whereas NTN1 overexpression had an opposing effect. Furthermore, the use of focal adhesion kinase (FAK) inhibitor decreased the proliferation of GC cells. It was also revealed that NTN1 markedly induced the phosphorylation of FAK, extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK), but did not induce the phosphorylation of P38. In addition, the expression of ERK and JNK was markedly inhibited by treatment with FAK inhibitor. Xenograft analysis using GC cells revealed that NTN1 overexpression promoted tumor growth. Furthermore, the expression of NTN1 in samples collected from nude mice was downregulated in the NTN1 knockdown group and upregulated in the NTN1 overexpression group compared with the control short hairpin RNA group. These results suggest that NTN1‑induced GC cell proliferation is mediated by activating ERK/MAPK signaling cascades via the distinct activation of FAK.

show abstract

Section: Introductionmentioning

confidence: 99%

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been revealed that almost 97% of the human genome sequence is transcribed into non-coding RNAs (ncRNAs), and long noncoding RNAs (lncRNAs) are proposed as valuable novel molecules because they are deregulated in many cancers [8,[22][23][24]. For example, Zhang R et al certified that lncRNA TP73-AS1 interacts with miR-142, thus modulating cell growth in brain glioma by activating the HMGB1/RAGE pathway [17].…”

Section: Discussionmentioning

confidence: 99%

“…The PI3K/AKT signaling pathway was proven important in the proliferation and metastasis of cancer cells [17]. Our literature research revealed that this is a classic pathway and significant for cancer research because it can promote progression and development of tumors.…”

mentioning

confidence: 97%

Long non-coding RNA CRNDE may be associated with poor prognosis by promoting proliferation and inhibiting apoptosis of cervical cancer cells through targeting PI3K/AKT

Yang¹,

Huang²,

Cao³

et al. 2018

neo

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs) are attracting more and more attention from researchers because they are relatively new factors in regulating biological processes in human cancers. The Colorectal Neoplasia Differentially Expressed (CRNDE) lncRNA is transcribed from chromosome 16 on the opposite strand to the neighboring IRX5 gene. It was originally discovered abnormally expressed in colorectal cancer (CRC) and was certified a critical biomarker in many cancers. However, its biological function and mechanism underlying the tumorigenesis of cervical cancer still require exploration. This study confirmed that CRNDE is markedly up-regulated in clinical tissues and cell lines of cervical cancer. The high expression of CRNDE positively correlates with advanced FIGO stage and lymph node metastasis. Furthermore, the overall survival rate in the group with highly expressed CRNDE was worse, and the high level of CRNDE may be regarded a prognostic factor because of its results from proportional hazard analysis. Loss-of-function assays revealed that CRNDE influences proliferation and apoptosis in cervical cancer cells, and Western blot assays revealed that the PI3K/AKT pathway was inactivated in response to CRNDE knockdown. Therefore, we conclude that CRNDE exerts oncogenic function in cervical cancer and should be further explored as a novel prognostic predictor.

show abstract

“…The constitutive activation of the PI3K/Akt signaling pathway has been noted during the malignant transformation of various cell lines and implicated in carcinogenesis and metastatic potential of human cancer (22). A previous study identified that PI3K/Akt modulated cancer metastasis via the regulation of EMT (23).…”

Section: Discussionmentioning

confidence: 99%

PIAS1 inhibited the metastasis of gastric cancer cell by epithelial-mesenchymal transition regulation within the inflammatory microenvironment

Wang

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Protein inhibitor of activated signal transducer and activator of transcription-1 (PIAS1) is an important regulator of the inflammatory signaling network, the expression of which was decreased in gastric cancer and implicated in the development of cancer. However, its mechanism has not been elucidated. The aim of the present study was to investigate the effect of PIAS1 on epithelial-mesenchymal transition (EMT) of gastric cancer cells within the inflammatory microenvironment. Recombinant adenovirus Ad5/F35-PIASl and Ad5/F35-null plasmids were constructed to transfect SGC7901 cells. Subsequently, these plasmids were confirmed by reverse transcription polymerase chain reaction and western blotting. The cells were treated with IL-6 or Ad5/F35-PIASl+IL-6, and the control cells were treated with Ad5/F35-null+IL-6. The morphological changes to the cells were observed using inverted microscopy. The effect of PIAS1 on cell migration and invasion was evaluated by scratch wound healing and Transwell chamber assays, and the protein expression of EMT markers and phosphatidylinositol 3-kinase (PI3K)/serine/threonine-protein kinase (Akt)/matrix metalloproteinase (MMP)-9 signaling pathway was examined by western blotting. Transfection with Ad5/F35-PIASl markedly increased the PIAS1 expression in SGC7901 cells. The cells acquired the more typical spindle-shape phenotype of mesenchymal cells following co-culture with IL-6; the cells co-cultured with IL-6 and Ad5/F35-PIASl acquired changes concordant with an epithelial phenotype. The overexpression of PIAS1 significantly decreased the migratory and invasive capacities of the SGC7901 cells (P<0.01). Western blotting indicated that the expression levels of E-cadherin protein in the cells treated with Ad5/F35-PIASl+IL-6 were increased significantly and the expression levels of zinc finger protein SNAI, Twist-related protein 1, vimentin and MMP-9, and the activation of PI3K/Akt proteins were decreased when compared with IL-6-or Ad5/F35-null+IL-6-treated cells (both P<0.01). PIAS1 may inhibit EMT in gastric cancer cells within the inflammatory microenvironment via the regulation of PI3K/Akt pathway activation, and may serve an important role in the inhibition of tumor invasion and metastasis with in this microenvironment. IntroductionGastric cancer is a common disease and a leading cause of cancer-associated mortality. According to a statistical study, ~70% of patients with gastric cancer in 2006 had lymph node metastasis at the time of diagnosis, leading to a median overall survival time of 16.7 months (1). Despite the standardization of surgical techniques and multimodal therapy, the postoperative survival of patients with advanced gastric cancer remains low in China due to the rates of invasion and metastasis (2).Epithelial-mesenchymal transition (EMT) is a process by which cells lose epithelial characteristics and acquire mesenchymal properties, including the loss of all cell-cell contact, increased motility and invasion (3). Previous studies have indicated that the EMT ...

show abstract

Netrin-1 promotes gastric cancer cell proliferation and invasion via the receptor neogenin through PI3K/AKT signaling pathway

Cited by 43 publications

References 33 publications

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

Netrin‑1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation

Long non-coding RNA CRNDE may be associated with poor prognosis by promoting proliferation and inhibiting apoptosis of cervical cancer cells through targeting PI3K/AKT

PIAS1 inhibited the metastasis of gastric cancer cell by epithelial-mesenchymal transition regulation within the inflammatory microenvironment

Contact Info

Product

Resources

About