title: Galectin-3 augments tumor initiating property and tumorigenicity of lung cancer through interaction with β-catenin.
abstract: 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.
authors: Department of Biotechnology and Laboratory Science in Medicine, and Immunity and Inflammation Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.|Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ROC.
authors: Ling-Yen
authors: LY
authors: Chung
authors: Institute of Marine Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, ROC.
authors: Shye-Jye
authors: SJ
authors: Tang
authors: Department of Biotechnology and Laboratory Science in Medicine, and Immunity and Inflammation Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.|Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ROC.
authors: Yi-Ching
authors: YC
authors: Wu
authors: Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, ROC.
authors: Guang-Huan
authors: GH
authors: Sun
authors: Division of Urology Surgery, Department of Surgery, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan, ROC.
authors: Huan-Yun
authors: HY
authors: Liu
authors: Department of Biotechnology and Laboratory Science in Medicine, and Immunity and Inflammation Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.|Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ROC.
authors: Kuang-Hui
authors: KH
authors: Sun
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002273:Carcinogens / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D037502:Galectin 3 / Q000032:analysis / Q000378:metabolism*; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000032:analysis / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D037502:Galectin 3; D051176:beta Catenin
keywords: cancer stem cells (CSCs); galectin-3; lung cancer; β-catenin