Mei-Chun Lin1, Miao-Juei Huang2, Chiung-Hui Liu3, Tsung-Lin Yang4, Min-Chuan Huang5. 1. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. 3. Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan. 4. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: yangtl@ntu.edu.tw. 5. Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: mchuang@ntu.edu.tw.
Abstract
OBJECTIVES: Oral squamous cell carcinoma (OSCC) is one of the leading cancers worldwide. Aberrant glycosylation affects many cellular properties in cancers, including OSCC. This study aimed to explore the role of N-acetylgalactosaminyltransferase 2 (GALNT2) in OSCC. MATERIALS AND METHODS: Immunohistochemistry was performed to study the expression of GALNT2 in an OSCC tissue microarray. Effects of GALNT2 overexpression and knockdown on cell migration and invasion were analyzed in SAS cells by transwell migration assay and matrigel invasion assay, respectively. The Vicia villosa agglutinin (VVA) pull down assay was conducted to detect changes in O-glycans on acceptor substrates of GALNT2. Cell signaling was analyzed by Western blotting. RESULTS: GALNT2 was overexpressed in 73% (35/48) of OSCC tissues. Moreover, GALNT2 expression was localized in the invasive front and increased in high grade OSCC. GALNT2 overexpression enhanced migration and invasion of SAS cells triggered by fetal bovine serum (FBS) and epidermal growth factor (EGF). In contrast, GALNT2 knockdown inhibited SAS cell migration and invasion. Furthermore, GALNT2 overexpression enhanced VVA binding to epidermal growth factor receptor (EGFR) and EGF-induced phosphorylation of EGFR and AKT. Conversely, GALNT2 knockdown decreased VVA binding and suppressed activity of EGFR and AKT. CONCLUSION: GALNT2 is frequently overexpressed in OSCC, especially in the carcinoma cells at the invasive front. GALNT2 overexpression enhances the invasive potential of OSCC cells via modifying O-glycosylation and activity of EGFR. These findings suggest that GALNT2 plays an important role in the invasive behavior of OSCC and that targeting GALNT2 could be a promising approach for OSCC therapy.
OBJECTIVES:Oral squamous cell carcinoma (OSCC) is one of the leading cancers worldwide. Aberrant glycosylation affects many cellular properties in cancers, including OSCC. This study aimed to explore the role of N-acetylgalactosaminyltransferase 2 (GALNT2) in OSCC. MATERIALS AND METHODS: Immunohistochemistry was performed to study the expression of GALNT2 in an OSCC tissue microarray. Effects of GALNT2 overexpression and knockdown on cell migration and invasion were analyzed in SAS cells by transwell migration assay and matrigel invasion assay, respectively. The Vicia villosa agglutinin (VVA) pull down assay was conducted to detect changes in O-glycans on acceptor substrates of GALNT2. Cell signaling was analyzed by Western blotting. RESULTS: GALNT2 was overexpressed in 73% (35/48) of OSCC tissues. Moreover, GALNT2 expression was localized in the invasive front and increased in high grade OSCC. GALNT2 overexpression enhanced migration and invasion of SAS cells triggered by fetal bovine serum (FBS) and epidermal growth factor (EGF). In contrast, GALNT2 knockdown inhibited SAS cell migration and invasion. Furthermore, GALNT2 overexpression enhanced VVA binding to epidermal growth factor receptor (EGFR) and EGF-induced phosphorylation of EGFR and AKT. Conversely, GALNT2 knockdown decreased VVA binding and suppressed activity of EGFR and AKT. CONCLUSION: GALNT2 is frequently overexpressed in OSCC, especially in the carcinoma cells at the invasive front. GALNT2 overexpression enhances the invasive potential of OSCC cells via modifying O-glycosylation and activity of EGFR. These findings suggest that GALNT2 plays an important role in the invasive behavior of OSCC and that targeting GALNT2 could be a promising approach for OSCC therapy.
Authors: John J Wallbillich; Paul Mh Tran; Shan Bai; Lynn Kh Tran; Ashok K Sharma; Sharad A Ghamande; Jin-Xiong She Journal: Am J Cancer Res Date: 2020-05-01 Impact factor: 6.166
Authors: Brittany Montesino; Agata Steenackers; Juan M Lozano; Geoffrey D Young; Nan Hu; Robert Sackstein; Kevin Brown Chandler Journal: Glycobiology Date: 2022-04-21 Impact factor: 4.313
Authors: Ieva Bagdonaite; Emil M H Pallesen; Mathias I Nielsen; Eric P Bennett; Hans H Wandall Journal: Adv Exp Med Biol Date: 2021 Impact factor: 3.650
Authors: Yin-Ling Wong; Ramanathan Anand; Kar Mun Yuen; Wan Mahadzir Wan Mustafa; Mannil Thomas Abraham; Keng Kiong Tay; Zainal Ariff Abdul Rahman; Yeng Chen Journal: Glycoconj J Date: 2021-02-06 Impact factor: 2.916