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 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 closely associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9 , the expression of which was regulated 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 b-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of b-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and suppressed invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with recurrence-free survival and hazard risk, suggesting that targeting b-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC.
저자
Ok-Seon Kwon [ College of NaturalSciences, Department of Life Sciences, Sogang University, Seoul, Republic of Korea ]
Jhingook Kim [ Department of Thoracic Surgery, Samsung Medical Center, SungkyunkwanUniversity, School of Medicine, Seoul, Republic of Korea ]
Hyuk-Jin Cha [ 차혁진 | College of NaturalSciences, Department of Life Sciences, Sogang University, Seoul, Republic of Korea ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.