<i>RACK1</i>is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer

Choi, Yi Young; Lee, Shin Yup; Lee, Won Kee; Jeon, Hyo Sung; Lee, Eung Bae; Lee, Hyun Cheol; Choi, Jin Eun; Kang, Hyo Gyoung; Lee, Eun Jin; Bae, Eun Young; Yoo, Seung Soo; Lee, Jaehee; Ick, Seung; Kim, Chang Ho; Kim, In San; Lee, Myung Hoon; Kim, Young Tae; Jheon, Sanghoon; Park, Jae Yong

doi:10.18632/oncotarget.2865

Cited by 15 publications

(20 citation statements)

References 40 publications

(36 reference statements)

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“…It has been suggested in previous studies that the dysregulation of RACK1 is involved in a variety of cancers, such as esophageal squamous cell carcinoma, lung cancer and ovarian cancer (10)(11)(12)(13). In the study by Peng et al, it was demonstrated that the enforced downregulation of RACK1 inhibited tumor xenograft growth in nude mice, and inhibited the proliferation and invasion of human glioma cells in vitro (14).…”

Section: Discussionmentioning

confidence: 99%

“…The receptor for activated C kinase 1 (RACK1) is a versatile scaffold protein involved in the regulation of a variety of cellular processes, including cell growth, migration, survival and metastasis (7)(8)(9). Previous studies have indicated that RACK1 is abnormally expressed in various malignant tumors, and its dysregulation may contribute to tumorigenesis (10)(11)(12)(13). Certain pathways have been demonstrated to be activated by RACK1, such as the Src/Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and the sonic hedgehog signaling pathway (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway

Yoshida

Jiang

2015

International Journal of Molecular Medicine

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Receptor for activated C kinase 1 (RACK1) and contactin-2 (CNTN2) are known to be abnormally expressed in gliomas; however, the association between RACK1 and CNTN2, and the effects of RACK1 and CNTN2 on glioma cell differentiation and the related molecular mechanisms remain largely unknown. The present study aimed to investigate the interaction between RACK1 and CNTN2, and to examine whether RACK1/CNTN2/receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) axis plays a role in glioma growth and differentiation. The results from western blot analysis revealed that the protein expression levels of RACK1 and CNTN2 were higher in high‑grade glioma tissues and cells, and lower in low-grade glioma tissues and cells. A co-immunoprecipitation assay demonstrated that RACK1 interacts with CNTN2, and RACK1 upregulated the expression of CNTN2. Gain-of‑function and loss-of‑function experiments indicated that both RACK1 and CNTN2 promoted glioma cell proliferation, inhibited glioma cell differentiation and activated the RTK/Ras/MAPK pathway. However, the effects of RACK1 on glioma cell proliferation, differentiation and the activation of the RTK/Ras/MAPK signaling pathway were abolished by the knockdown of CNTN2 using siRNA. In Therefore, the findings of this study firstly demonstrate that RACK1 interacts with CNTN2, and that the effects of RACK1 on glioma cell growth and differentiation are mediated by CNTN2. The RACK1/CNTN2/RTK/Ras/MAPK axis exists in glioma cells, and it may be a potential therapeutic target in gliomas.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway

Yoshida

Jiang

2015

International Journal of Molecular Medicine

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“…In our previous study, promoter assay and electrophoretic mobility shift assay (EMSA) revealed that the rs3756585 T‐to‐G change increased transcription factor binding and promoter activity of GNB2L1 . This study suggests that polymorphisms of the two genes enhance the prognostic ability of pathologic stage in the novel prognosis‐prediction model. Further studies are needed to understand the roles of the two genes in lung cancer and to clarify the association between the SNPs and prognosis.…”

Section: Discussionmentioning

confidence: 70%

Development of a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage in stage I non‐small cell lung cancer: A multicenter study

Lee

Choi

et al. 2017

Thoracic Cancer

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BackgroundThis multicenter study was performed to develop a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non‐small cell lung cancer (NSCLC) patients.MethodsA replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression.ResultsAmong the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis‐prediction model, we categorized patients into low, intermediate, and high‐risk groups, which had greater accuracy in predictive ability (log‐rank statistics = 54.66) than the conventional tumor node metastasis staging (log‐rank statistics = 39.56). Next, we generated a prognosis‐prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high‐risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy.ConclusionsThis prognosis‐prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.

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“…We selected SNPs for the present study using public databases, as described previously [13,14]. Briefly, we selected 1784 candidate genes involved in cancer-related pathways from the database of SABiosciences (www.sabiosciences.com/Cancer.php; online supplementary table S1).…”

Section: Selection Of Polymorphisms and Genotypingmentioning

confidence: 99%

Polymorphisms in cancer-related pathway genes and lung cancer

et al. 2016

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We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population.A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication.Among the 68 SNPs, three SNPs (corepressor interacting with RBPJ 1 (CIR1) rs13009079T>C, ribonucleotide reductase M1 (RRM1) rs1465952T>C and solute carrier family 38, member 4 (SLC38A4) rs2429467C>T) consistantly showed significant associations with lung cancer in the replication study. In combined analysis, adjusted odds ratio for CIR1 rs13009079T>C, RRM1 rs1465952T>C and SLC38A4 rs2429467C>T were 0.69, 0.71 and 0.73, respectively (p=4×10, 0.01 and 0.001, respectively) under the dominant model. The relative mRNA expression level of CIR1 was significantly associated with rs13009079T>C genotypes in normal lung tissues (p=0.03).These results suggest that the three SNPs, particularly CIR1 rs13009079T>C, may play a role in the pathogenesis of lung cancer.

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RACK1is a candidate gene associated with the prognosis of patients with early stage non-small cell lung cancer

Cited by 15 publications

References 40 publications

RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway

RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway

Development of a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage in stage I non‐small cell lung cancer: A multicenter study

Polymorphisms in cancer-related pathway genes and lung cancer

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