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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]
- Issue Date
- Oncotarget, 6(39), 41916-41928
- Article Type
- Animal Experiment; Animal Model; Beta Catenin; Cancer Prognosis; Cancer Survival; Controlled Study; Down-Regulation; Enzyme Activity; Galnac-T14; Genomics; HOXB9; Hoxb9 Protein; Invasion; Lung Adenocarcinoma; Lung Metastasis; Male; Metastasis; Microarray Analysis; Mouse; N Acetylgalactosaminyltransferase; Non-Human; Oncoprotein; Phenotype; Protein Expression; Protein Stability; Protein Targeting; Recurrence Free Survival; Sensitivity Analysis; Unclassified Drug; Upregulation; Wnt Protein; WNT/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.
- Impact Journals LLC
- Related Researcher
Koo, Jae Hyung
The Koo Lab - ChemoReception Laboratory(CRLab)
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