Role of Recepteur D'origine Nantais on Gastric Cancer Development and Progression

Yang, Sung Yeul; Nguyen, Thi Phuong; Ung, Trong Thuan; Jung, Young Do

doi:10.4068/cmj.2017.53.3.178

Cited by 5 publications

(6 citation statements)

References 55 publications

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“…5a, b). MST1R was also known as c-Met-related tyrosine kinase, and normally harbored activation/gain mutations and/or overexpression in other cancer types [40][41][42][43] . In addition to playing an oncogenic role as tyrosine kinase to enhance activation of Ras/MAPK and other signaling cascades, MST1R also plays a vital function in host defense against viral infection, including Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) 6,44,45 .…”

Section: Resultsmentioning

confidence: 99%

“…However, different subtypes of NPC also share some common features, such as defective G1-S checkpoint surveillance, activated NF-κB signaling, aberrant RTKs and chromatin remodeling. Of note, one of the most notable common features is that they all lose MST1R at an extreme high frequency (55.6%), indicating that MST1R may act as a tumor suppressor in NPC, contrary to the carcinogenic effects of MST1R in other types of cancer [40][41][42][43] . It has been reported that MST1R is an NPC susceptibility gene associated with MST1R/14-3-3 interaction networks in the response to EBV infection, rather than functions as a tyrosine kinase that promotes proliferation and migration 6 .…”

Section: Discussionmentioning

confidence: 99%

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Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Ding¹,

Chen

Rajendran³

et al. 2021

Nat Commun

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Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Ding¹,

Chen

Rajendran³

et al. 2021

Nat Commun

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“…Ron, also known as MST1R, is an RTK from the Met proto-oncogene family; its dimerization and subsequent phosphorylation activates classical downstream signaling pathways, including MAPK, Jak/Stat3 and PI3K/Akt ( 31 ). Previous studies have demonstrated that knockdown of Ron by small interfering (si)RNA could suppress tumor cell migration and invasion, induce apoptosis, and arrest the cell cycle at S phase in AGS cells and G 2 /M phase in MKN28 cells ( 31 , 32 ). In addition, Ron expression has been significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway

Zhang

et al. 2019

Int J Oncol

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Emerging studies have reported that coatomer protein complex subunit β2 (COPB2) is overexpressed in several types of malignant tumor; however, to the best of our knowledge, no studies regarding COPB2 in gastric cancer have been published thus far. Therefore, the present study aimed to determine the significance and function of COPB2 in gastric cancer. COPB2 expression in gastric cancer cell lines was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. In addition, lentivirus-short hairpin RNA (shRNA) COPB2 (Lv-shCOPB2) was generated and used to infect BGC-823 cells to analyze the effects of COPB2 on the cancerous phenotype. The effects of shRNA-mediated COPB2 knockdown on cell proliferation were detected using MTT, 5-bromo-2-deoxyuridine and colony formation assays. In addition, the effects of COPB2 knockdown on apoptosis were analyzed by flow cytometry. Nude mice and fluorescence imaging were used to characterize the regulation of tumor growth in vivo, and qPCR and immunohistochemistry were subsequently conducted to analyze COPB2 expression in xenograft tumor tissues. Furthermore, a receptor tyrosine kinase (RTK) signaling pathway antibody array was used to explore the relevant molecular mechanisms underlying the effects of COPB2 knockdown. The results revealed that COPB2 mRNA was abundantly overexpressed in gastric cancer cell lines, whereas knockdown of COPB2 significantly inhibited cell growth and colony formation ability, and led to increased cell apoptosis in vitro. The tumorigenicity assay revealed that knockdown of COPB2 reduced tumor growth in nude mice, and fluorescence imaging indicated that the total radiant efficiency of mice in the Lv-shCOPB2-infected group was markedly reduced compared with the mice in the Lv-shRNA control-infected group in vivo. The antibody array assay revealed that the levels of phosphorylation in 23 target RTKs were significantly reduced: In conclusion, COPB2 was highly expressed in gastric cancer cell lines, and knockdown suppressed colony formation and promoted cell apoptosis via inhibiting the RTK signaling and its downstream signaling cascade molecules. Therefore, COPB2 may present a valuable target for gene silencing strategy in gastric cancer.

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“…The MET receptor signaling pathway is frequently overactivated in gastric cancer [6,8]. Another relevant RTK is the Recepteur d'Origine Nantais (RON) (also known as macrophage-stimulating protein receptor (MSPR) or MST1R) which commonly shows aberrant activation in various tumors due to overexpression and generation of oncogenic variants [9,10]. Alterations in the cellular glycosylation has been shown to modulate the activation of MET and RON in GC [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Effect of Increased α2,3-Sialylation on RTK Activation in MKN45 Gastric Cancer Spheroids Treated with Crizotinib

Balmaña

Diniz

Feijão

et al. 2020

IJMS

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In the scenario of personalized medicine, targeted therapies are currently the focus of cancer drug development. These drugs can block the growth and spread of tumor cells by interfering with key molecules involved in malignancy, such as receptor tyrosine kinases (RTKs). MET and Recepteur d’Origine Nantais (RON), which are RTKs frequently overactivated in gastric cancer, are glycoprotein receptors whose activation have been shown to be modulated by the cellular glycosylation. In this work, we address the role of sialylation in gastric cancer therapy using an innovative 3D high-throughput cell culture methodology that mimics better the in vivo tumor features. We evaluate the response to targeted treatment of glycoengineered gastric cancer cell models overexpressing the sialyltransferases ST3GAL4 or ST3GAL6 by subjecting 3D spheroids to the tyrosine kinase inhibitor crizotinib. We show here that 3D spheroids of ST3GAL4 or ST3GAL6 overexpressing MKN45 gastric cancer cells are less affected by the inhibitor. In addition, we disclose a potential compensatory pathway via activation of the Insulin Receptor upon crizotinib treatment. Our results suggest that cell sialylation, in addition of being involved in tumor progression, could play a critical role in the response to tyrosine kinase inhibitors in gastric cancer.

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Role of Recepteur D'origine Nantais on Gastric Cancer Development and Progression

Cited by 5 publications

References 55 publications

Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway

Analysis of the Effect of Increased α2,3-Sialylation on RTK Activation in MKN45 Gastric Cancer Spheroids Treated with Crizotinib

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