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      KCI등재 SCOPUS SCIE

      LETM1 Promotes Gastric Cancer Cell Proliferation, Migration, and Invasion via the PI3K/Akt Signaling Pathway

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      https://www.riss.kr/link?id=A106911985

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      다국어 초록 (Multilingual Abstract)

      Purpose: Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role ...

      Purpose: Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells.
      Materials and Methods: The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting.
      Results: The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway.
      Conclusions: LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.

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      참고문헌 (Reference)

      1 Newton AC, "Turning off AKT : PHLPP as a drug target" 54 : 537-558, 2014

      2 Hsieh HL, "Tumor progression-dependent angiogenesis in gastric cancer and its potential application" 11 : 686-704, 2019

      3 Dassen AE, "Trends in incidence, treatment and survival of gastric adenocarcinoma between 1990 and 2007 : a population-based study in the Netherlands" 46 : 1101-1110, 2010

      4 Vivanco I, "The phosphatidylinositol 3-Kinase AKT pathway in human cancer" 2 : 489-501, 2002

      5 Chen L, "The expression of LETM1 in gastric cancer and its correlation with prognosis" 54 : 1430-1434, 2019

      6 Bykov VJ, "Targeting mutant p53 for efficient cancer therapy" 18 : 89-102, 2018

      7 Hwang SK, "Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1" 5 : e12535-, 2010

      8 Huang B, "Suppression of LETM1 by siRNA inhibits cell proliferation and invasion of bladder cancer cells" 38 : 2935-2940, 2017

      9 Kobayashi I, "Significance of Akt phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma" 73 : 8-17, 2006

      10 Soussi T, "Shaping genetic alterations in human cancer : the p53 mutation paradigm" 12 : 303-312, 2007

      1 Newton AC, "Turning off AKT : PHLPP as a drug target" 54 : 537-558, 2014

      2 Hsieh HL, "Tumor progression-dependent angiogenesis in gastric cancer and its potential application" 11 : 686-704, 2019

      3 Dassen AE, "Trends in incidence, treatment and survival of gastric adenocarcinoma between 1990 and 2007 : a population-based study in the Netherlands" 46 : 1101-1110, 2010

      4 Vivanco I, "The phosphatidylinositol 3-Kinase AKT pathway in human cancer" 2 : 489-501, 2002

      5 Chen L, "The expression of LETM1 in gastric cancer and its correlation with prognosis" 54 : 1430-1434, 2019

      6 Bykov VJ, "Targeting mutant p53 for efficient cancer therapy" 18 : 89-102, 2018

      7 Hwang SK, "Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1" 5 : e12535-, 2010

      8 Huang B, "Suppression of LETM1 by siRNA inhibits cell proliferation and invasion of bladder cancer cells" 38 : 2935-2940, 2017

      9 Kobayashi I, "Significance of Akt phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma" 73 : 8-17, 2006

      10 Soussi T, "Shaping genetic alterations in human cancer : the p53 mutation paradigm" 12 : 303-312, 2007

      11 Piao L, "Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis" 21 : 767-777, 2009

      12 Yu HG, "Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death" 122 : 433-443, 2008

      13 Elmenier FM, "Phosphatidylinositol 3 kinase(PI3K)inhibitors as new weapon to combat cancer" 183 : 111718-, 2019

      14 Burris HA 3rd, "Overcoming acquired resistance to anticancer therapy : focus on the PI3K/AKT/mTOR pathway" 71 : 829-842, 2013

      15 Wu CW, "Nodal dissection for patients with gastric cancer : a randomised controlled trial" 7 : 309-315, 2006

      16 Polivka J Jr, "Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway" 142 : 164-175, 2014

      17 Zhang Y, "Long noncoding RNA SNHG1 promotes cell proliferation through PI3K/AKT signaling pathway in pancreatic ductal adenocarcinoma" 9 : 2713-2722, 2018

      18 Li N, "LETM1 overexpression is correlated with the clinical features and survival outcome of breast cancer" 8 : 12893-12900, 2015

      19 Li Y, "LETM1 is required for mitochondrial homeostasis and cellular viability(Review)" 19 : 3367-3375, 2019

      20 Piao L, "LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma" 215 : 152437-, 2019

      21 Piao L, "LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma" 19 : 898-, 2019

      22 Hart L, "LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome : implications for dissecting the underlying pathomechanisms in this condition" 7 : 535-545, 2014

      23 Xu J, "Knockdown of LETM1 inhibits proliferation and metastasis of human renal cell carcinoma cells" 16 : 6377-6382, 2018

      24 Yang Z, "Identification of LETM1 as a marker of cancer stem-like cells and predictor of poor prognosis in esophageal squamous cell carcinoma" 81 : 148-156, 2018

      25 Kim C, "How prognostic and predictive biomarkers are transforming our understanding and management of advanced gastric cancer" 19 : 1046-1055, 2014

      26 Chen L, "High expression of leucine zipper-EF-hand containing transmembrane protein 1 predicts poor prognosis in head and neck squamous cell carcinoma" 2014 : 850316-, 2014

      27 Wang F, "Helicobacter pylori-induced gastric inflammation and gastric cancer" 345 : 196-202, 2014

      28 Suerbaum S, "Helicobacter pylori infection" 347 : 1175-1186, 2002

      29 Van Cutsem E, "Gastric cancer" 388 : 2654-2664, 2016

      30 Oliveira C, "Familial gastric cancer : genetic susceptibility, pathology, and implications for management" 16 : e60-e70, 2015

      31 Ye B, "Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis" 25 : 627-636, 2012

      32 Puneet, "Epigenetic mechanisms and events in gastric cancer-emerging novel biomarkers" 24 : 757-770, 2018

      33 Crew KD, "Epidemiology of gastric cancer" 12 : 354-362, 2006

      34 Szász AM, "Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1, 065 patients" 7 : 49322-49333, 2016

      35 Ferlay J, "Cancer incidence and mortality worldwide : sources, methods and major patterns in GLOBOCAN 2012" 136 : E359-E386, 2015

      36 Piao L, "Association of LETM1 and MRPL36 contributes to the regulation of mitochondrial ATP production and necrotic cell death" 69 : 3397-3404, 2009

      37 Ogawara Y, "Akt enhances Mdm2-mediated ubiquitination and degradation of p53" 277 : 21843-21850, 2002

      38 Uhlen M, "A pathology atlas of the human cancer transcriptome" 357 : eaan2507-, 2017

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2017-05-01 평가 SCIE 등재 (기타) KCI등재
      2015-07-31 학술지명변경 한글명 : 대한위암학회지 -> Journal of Gastric Cancer KCI등재
      2015-07-30 학술지명변경 외국어명 : Journal of Korean Gastric Cancer Association -> Journal of Gastric Cancer KCI등재
      2013-11-01 평가 SCOPUS 등재 (등재유지) KCI등재
      2013-01-01 평가 등재후보학술지 유지 (기타) KCI등재후보
      2012-01-01 평가 등재후보학술지 유지 (기타) KCI등재후보
      2011-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2009-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      학술지 인용정보
      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.46 0.24 0.35
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.31 0.37 0.461 0.05
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