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GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma

GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma
Kwon, OS[Kwon, Ok-Seon]Oh, E[Oh, Ensel]Park, JR[Park, Jeong-Rak]Lee, JS[Lee, Ji-Seon]Bae, GY[Bae, Gab-Yong]Koo, JH[Koo, Jae-Hyung]Kim, H[Kim, Hyongbum]Choi, YL[Choi, Yoon-La]Choi, YS[Choi, Young Soo]Kim, J[Kim, Jhingook]Cha, HJ[Cha, Hyuk-Jin]
DGIST Authors
Koo, JH[Koo, Jae-Hyung]
Issued Date
Article Type
Animal ExperimentAnimal ModelBeta CateninCancer PrognosisCancer SurvivalControlled StudyDown-RegulationEnzyme ActivityGalnac-T14GenomicsHOXB9Hoxb9 ProteinInvasionLung AdenocarcinomaLung MetastasisMaleMetastasisMicroarray AnalysisMouseN AcetylgalactosaminyltransferaseNon-HumanOncoproteinPhenotypeProtein ExpressionProtein StabilityProtein TargetingRecurrence Free SurvivalSensitivity AnalysisUnclassified DrugUpregulationWnt ProteinWNT/TCF Pathway
While metastasis, the main cause of lung cancer-related death, has been extensively studied, the underlying molecular mechanism remains unclear. A previous clinicogenomic study revealed that expression of N-acetylgalactosaminyltransferase (GalNAc-T14), is highly inversely correlated with recurrence-free survival in those with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism(s) has not been determined. Here, we showed that GalNAc-T14 expression was positively associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9, the expression of which was increased in a GalNAc- T14-dependent manner, played an important role in metastasis. GalNAc-T14 increased the sensitivity of the WNT response and increased the stability of the ß-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of ß-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with reduced recurrence-free survival and increased hazard risk, suggesting that targeting ß-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC.
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Related Researcher
  • 구재형 Koo, JaeHyung 뉴바이올로지학과
  • Research Interests 장내미생물/감염균 유래 대사체를 통한 신경염증; 알츠하이머병; 우울증; 당뇨/비만; 대사체/수용체 상호작용에 의한 대사연구
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Department of New Biology Brain-Immune Axis Laboratory 1. Journal Articles


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