Galectin-3 augments tumor initiating property and tumorigenicity of lung cancer through interaction with β-catenin.
Galectin-3 augments tumor initiating property and tumorigenicity of lung cancer through interaction with β-catenin.
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DOI：
10.18632/oncotarget.3210
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Sun KH
中科院分区：
文献类型：
--
作者：
Chung LY;Tang SJ;Wu YC;Sun GH;Liu HY;Sun KH
癌症干细胞（CSC）是由肿瘤中罕见的细胞亚群组成，已被认为是导致高复发率和化疗耐药性的原因。半乳糖凝集素在与肿瘤侵袭性相关的癌症中高度表达。半乳糖凝集素还可以促进癌细胞对化疗的抗性。然而，半乳糖凝集素在CSC中的作用仍然未知。在这项研究中，球体形成用于富集H1299人肺CSC，其具有自我更新能力，晚期致瘤潜力，并且高度表达干/祖细胞标志物，如Oct 4，Sox 2，Nanog和CD 133。在肺CSC中发现了一种新的干细胞候选分子半乳糖凝集素-3。半乳糖凝集素-3的表达在连续传代的肺癌球体中强烈增加，但其在H1299单层或球体中的抑制导致小鼠中干细胞相关基因、球体形成能力、致瘤性、化学抗性和肿瘤起始的表达降低。值得注意的是，半乳糖凝集素-3在A549肺癌细胞中的过表达促进了CSC的形成，A549肺癌细胞作为肿瘤球生长的能力较低。β-连环蛋白活性在H1299球体中增加，并被半乳糖凝集素-3抑制所抵消。因此，半乳糖凝集素-3可能作为辅因子通过与β-连环蛋白相互作用来增强干性相关基因的转录活性。此外，galectin-3表达与肺癌组织中的肿瘤进展以及β-catenin和CSC标志物CD 133的表达相关。靶向半乳糖凝集素-3信号转导可能通过抑制干细胞样特性为肺癌治疗提供新的策略。
Cancer stem cells (CSCs) are comprised of a rare sub-population of cells in tumors that have been proposed to be responsible for high recurrence rates and resistance to chemotherapy. Galectins are highly expressed in cancers that correlate with the aggressiveness of tumors. Galectins may also promote the resistance of cancer cells to chemotherapy. However, the role of galectins in CSCs remains unknown. In this study, sphere formation was used to enrich H1299 human lung CSCs that had self-renewal ability, advanced tumorigenic potential, and that highly expressed stem/progenitor cell markers such as Oct4, Sox2, Nanog, and CD133. A novel candidate molecule, galectin-3, for stemness was found in lung CSCs. The expression of galectin-3 robustly increased in lung cancer spheres over serial passages, but its suppression in the H1299 monolayer or spheres resulted in reduced expression of stemness-related genes, sphere-forming ability, tumorigenicity, chemoresistance, and tumor initiation in mice. Notably, the overexpression of galectin-3 in A549 lung cancer cells, which have low capability to grow as tumor spheres, promoted CSC formation. β-catenin activity was increased in H1299 spheres and counteracted by galectin-3 suppression. Thus, galectin-3 may act as a cofactor by interacting with β-catenin to augment the transcriptional activities of stemness-related genes. Furthermore, galectin-3 expression correlated with tumor progression and expressions of β-catenin and CSC marker CD133 in lung cancer tissues. Targeting galectin-3 signaling may provide a new strategy for lung cancer treatment by inhibiting stem-like properties.
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