Song Kyoung Jin, Jeon Seong Kook, Moon Su Bin, Park Jin Suk, Kim Jang Seong, Kim Jeongkwon, Kim Sumin, An Hyun Joo, Ko Jeong-Heon, Kim Yong-Sam
Genome Editing Research Center, KRIBB, Daejeon, South Korea.
Department of Chemistry, Chungnam National University, Daejeon, South Korea.
Oncotarget. 2017 Jun 27;8(26):42238-42251. doi: 10.18632/oncotarget.15034.
Anoikis is a form of anchorage-dependent apoptosis, and cancer cells adopt anokis-resistance molecular machinery to conduct metastasis. Here, we report that N-acetylglucosaminyltransferase V gene expression confers anoikis resistance during cancer progression. Overexpression of N-acetylglucosaminyltransferase V protected detached cancer cells from apoptotic death, and suppression or knockout of the gene sensitized cancer cells to the apoptotic death. The gene expression also stimulated anchorage-dependent as well as anchorage-independent colony formation of cancer cells following anoikis stress treatments. Importantly, treatment with the lectin from Sambucus sieboldiana significantly sensitized anoikis-induced cancer cell deaths in vitro as well as in vivo. We propose that the lectin alone or an engineered form could offer a new therapeutic treatment option for cancer patients with advanced tumors.
失巢凋亡是一种依赖锚定的细胞凋亡形式，癌细胞采用抗失巢凋亡分子机制来进行转移。在此，我们报告N-乙酰葡糖胺基转移酶V基因表达在癌症进展过程中赋予了抗失巢凋亡能力。N-乙酰葡糖胺基转移酶V的过表达保护脱离的癌细胞免于凋亡死亡，而该基因的抑制或敲除使癌细胞对凋亡死亡敏感。该基因表达还在失巢凋亡应激处理后刺激了癌细胞的锚定依赖性和非锚定依赖性集落形成。重要的是，用接骨木凝集素处理在体外和体内均显著使失巢凋亡诱导的癌细胞死亡敏感化。我们提出，单独的凝集素或工程化形式可为晚期肿瘤癌症患者提供一种新的治疗选择。
