Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway

Zhang, Yan; Chen, Peisheng; Yin, Wei Hsian; Ji, Yiqin; Shen, Qin; Ni, Qingfeng

doi:10.1016/j.humpath.2017.10.034

Cited by 45 publications

(42 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nectin-4 is upregulated in various cancers, such as breast 46 , lung 47 , ovarian 48 , pancreatic 49 , gallbladder 50 , and gastric cancer 51 , and promotes cancer cell proliferation and metastasis 47,50,52,53 . The PI3K-AKT signalling pathway is implicated in these roles of nectin-4 through activation of the Wnt-β-catenin and Rac small G protein signalling pathways 51,54 . In addition, breast cancer cells cultured in soft agar express nectin-4 and nectin-1 that trans -interact each other in a heterophilic manner, and nectin-4 also trans -interacts in a homophilic manner 52 .…”

Section: Introductionmentioning

confidence: 99%

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Kedashiro

Mizutani

Takai

2019

Sci Rep

View full text Add to dashboard Cite

Nectin-4 cell adhesion molecule and ErbB2 tyrosine kinase receptor are upregulated in many cancers, including breast cancer, and promote cancer cell proliferation and metastasis. Using human breast cancer cell lines T47D and SUM190-PT, in which both nectin-4 and ErbB2 were upregulated, we showed here that nectin-4 cis-interacted with ErB2 and enhanced its dimerization and activation, followed by the activation of the phosphoinositide 3-kinase-AKT signalling pathway for DNA synthesis. The third immunoglobulin-like domain of nectin-4 cis-interacted with domain IV of ErbB2. This region differs from the trastuzumab-interacting region but is included in the trastuzumab-resistant splice variants of ErbB2, p95-ErbB2 and ErbB2ΔEx16. Nectin-4 also cis-interacted with these trastuzumab-resistant splice variants and enhanced the activation of the phosphoinositide 3-kinase-AKT signalling pathway for DNA synthesis. In addition, nectin-4 enhanced the activation of the p95-ErbB2-induced JAK-STAT3 signalling pathway, but not the ErbB2- or ErbB2ΔEx16-induced JAK-STAT3 signalling pathway. These results indicate that nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants and enhances the activation of these receptors and downstream signalling pathways in a novel mechanism.

show abstract

Section: Introductionmentioning

confidence: 99%

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Kedashiro

Mizutani

Takai

2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In human carcinogenesis, the PI3K-Akt signaling pathway inhibited the expression of tumor suppressor gene E-cadherin, which led to tumor cell epithelial mesenchymal transition and metastasis [ 20 – 22 ]. Previous studies have revealed that the PI3K-Akt signaling pathway plays a crucial role in the progression and metastasis of lung cancer [ 23 ], ovarian cancer [ 18 ], nasopharyngeal carcinoma [ 24 ], prostate cancer [ 25 ], colorectal cancer [ 26 ], and gastric cancer [ 27 ]. The present study further supports and confirms the important role of the PI3K-Akt signaling pathway in NM patients, which is novel, and to date, there has been no report in the literature.…”

Section: Discussionmentioning

confidence: 99%

Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing

Zhao

Cui

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

Background This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM). Methods A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software. Results The most common mutated gene was TP53 (54/62; 87.10%), followed by EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway. Conclusions This study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.

show abstract

“…In human carcinogenesis, the PI3K-Akt signaling pathway inhibited the expression of tumor suppressor gene Ecadherin, which led to tumor cell epithelial mesenchymal transition and metastasis [20][21][22]. Previous studies have revealed that the PI3K-Akt signaling pathway plays a crucial role in the progression and metastasis of lung cancer [23], ovarian cancer [18], nasopharyngeal carcinoma [24], prostate cancer [25], colorectal cancer [26], and gastric cancer [27]. The present study further supports and confirms the important role of the PI3K-Akt signaling pathway in NM patients, which is novel, and to date, there has been no report in the literature.…”

Section: Discussionmentioning

confidence: 99%

Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing

Zhao

Cui

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: This study profiled the somatic gene mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM). Methods: A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were blasted in GenBank and bioinformatically analyzed. Results: Cancer-associated gene mutations occurred in all 62 CSF ctDNA samples in TP53 (54/62; 87.10%), EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes enriched by the KEGG pathway analysis were the PI3K-Akt, which included the genes of TP53, EGFR, PTEN, KIT and KDR. After receiving intrathecal and systemic chemotherapy, the ERK1/2 signaling pathways of these CSF samples were activated. Furthermore, the CNVs of these genes were also identified in these 62 samples. Conclusions: This study identified gene mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway.

show abstract

Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway

Cited by 45 publications

References 31 publications

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing

Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing

Contact Info

Product

Resources

About