title: Autocrine Semaphorin3A signaling is essential for the maintenance of stem-like cells in lung cancer.
abstract: Cancer stem-like cells (CSCs) exist in tumor tissues composed of heterogeneous cell population and are characterized by their self-renewal capacity and tumorigenicity. Many studies demonstrate that eradication of CSCs prevents development and recurrences of tumor; yet, molecules critical for the maintenance of CSCs have not been completely understood. We previously reported that Semaphorin3A (Sema3a) knockdown suppressed the tumorigenicity and proliferative capacity of Lewis lung carcinoma (LLC) cells. Therefore, we identified Sema3a as an essential factor for the establishment or maintenance of CSCs derived from LLC (LLC-stem cell). shRNA against Sema3a was introduced into LLC cells to establish a LLC-stem cell line and its effects on tumorigenesis, sphere formation, and mTORC1 activity were tested. Sema3a knockdown completely abolished tumorigenicity and the sphere-formation and self-renewal ability of LLC-stem cells. The Sema3a knockdown was also associated with decreased expression of mRNA for stem cell markers. The self-renewal ability abolished by Sema3a knockdown could not be recovered by exogenous addition of recombinant SEMA3A. In addition, the activity of mammalian target of rapamycin complex 1 (mTORC1) and the expression of its substrate p70S6K1 were also decreased. These results demonstrate that Sema3a is a potential therapeutic target in eradication of CSCs.
authors: Department of Pharmacology, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata-city, Niigata 956-8603, Japan.
authors: Daisuke
authors: D
authors: Yamada
authors: Department of Pharmacology, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata-city, Niigata 956-8603, Japan.
authors: Kensuke
authors: K
authors: Takahashi
authors: Department of Pharmacology, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata-city, Niigata 956-8603, Japan.
authors: Kohichi
authors: K
authors: Kawahara
authors: Department of Pharmacology, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata-city, Niigata 956-8603, Japan. Electronic address: maeda@nupals.ac.jp.
authors: Takehiko
authors: T
authors: Maeda
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D040121:Semaphorin-3A / Q000378:metabolism*
chemical_list: D040121:Semaphorin-3A
keywords: Cancer stem-like cell; Lung cancer; Semaphorin3A; mTOR signaling