https://scholars.lib.ntu.edu.tw/handle/123456789/462393
標題: | β1, 4-N-acetylgalactosaminyltransferase III modulates cancer stemness through EGFR signaling pathway in colon cancer cells | 作者: | Che M.-I. JOHN HUANG JI-SHIANG HUNG Lin Y.-C. Huang M.-J. HONG-SHIEE LAI WEN-MING HSU JIN-TUNG LIANG MIN-CHUAN HUANG |
公開日期: | 2014 | 出版社: | Impact Journals LLC | 卷: | 5 | 期: | 11 | 起(迄)頁: | 3673-3684 | 來源出版物: | Oncotarget | 摘要: | Cancer stem cells are cancer cells characterized with tumor initiating capacity. β1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) synthesizes GalNAcβ1-4GlcNAc (LacdiNAc) which contributes to self-renewal of mouse embryonic stem cells. We previously showed that B4GALNT3 overexpression enhances colon cancer cell malignant phenotypes in vitro and in vivo. However, the role of B4GALNT3 in cancer stemness remains unclear. We found that B4GALNT3 expression was positively correlated with advanced stages and poor survival in colorectal cancer patients. Knockdown of B4GALNT3 using small interfering (si) RNAs in colon cancer cell lines (HCT116, SW480, HCT15, and HT29 cells) decreased sphere formation and the expression of stem cell markers, OCT4 and NANOG. The expression of B4GALNT3 was upregulated in colonospheres. Interestingly, we found that B4GALNT3 primarily modified N-glycans of EGFR with LacdiNAc by Wisteria floribunda agglutinin (WFA) pull down assays. B4GALNT3 knockdown suppressed EGF-induced phosphorylation of EGFR and its downstream signaling molecules. Furthermore, EGF-induced degradation of EGFR was facilitated. In addition, EGF-induced migration and invasion were significantly suppressed by B4GALNT3 knockdown. Taken together, these data suggest B4GALNT3 regulates cancer stemness and the invasive properties of colon cancer cells through modifying EGFR glycosylation and signaling. Our results provide novel insights into the role of LacdiNAc in colorectal cancer development. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84903527115&doi=10.18632%2foncotarget.1981&partnerID=40&md5=cc8e3c92eee6d6a8d39ccd6ff52c38ac https://scholars.lib.ntu.edu.tw/handle/123456789/462393 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.1981 | SDG/關鍵字: | beta1 n acetylgalactosaminyltransferase III; epidermal growth factor receptor; n acetylgalactosaminyltransferase; octamer transcription factor 4; small interfering RNA; transcription factor NANOG; unclassified drug; beta-1,4-N-acetylgalactosaminyltransferase III, human; EGFR protein, human; epidermal growth factor receptor; n acetylgalactosaminyltransferase; article; cancer cell line; cancer staging; cell migration; colon cancer; colon carcinogenesis; controlled study; disease activity; enzyme activity; enzyme glycosylation; human; human cell; molecular dynamics; molecular pathology; protein degradation; protein determination; protein expression; protein function; protein phosphorylation; signal transduction; survival rate; tumor invasion; upregulation; cancer stem cell; cell proliferation; colon tumor; enzymology; gene silencing; genetics; glycosylation; HCT116 cell line; HT 29 cell line; metabolism; pathology; physiology; signal transduction; tumor cell line; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Gene Knockdown Techniques; Glycosylation; HCT116 Cells; HT29 Cells; Humans; N-Acetylgalactosaminyltransferases; Neoplastic Stem Cells; Receptor, Epidermal Growth Factor; Signal Transduction |
顯示於: | 醫學系 |
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