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Title: mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling

Abstract

Aberration of signaling pathways by genetic mutations or alterations in the surrounding tissue environments can result in tumor development or metastasis. However, signaling molecules responsible for these processes have not been completely elucidated. Here, we used mouse Lewis lung carcinoma cells (LLC) to explore the mechanism by which the oncogenic activity of Semaphorin3A (Sema3A) signaling is regulated. Sema3A knockdown by shRNA did not affect apoptosis, but decreased cell proliferation in LLCs; both the mammalian target of rapamycin complex 1 (mTORC1) level and glycolytic activity were also decreased. In addition, Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation by oligomycin, but conferred resistance to decreased cell viability induced by glucose starvation. Furthermore, recombinant SEMA3A rescued the attenuation of cell proliferation and glycolytic activity in LLCs after Sema3A knockdown, whereas mTORC1 inhibition by rapamycin completely counteracted this effect. These results demonstrate that Sema3A signaling exerts its oncogenic effect by promoting an mTORC1-mediated metabolic shift from oxidative phosphorylation to aerobic glycolysis. -- Highlights: •Sema3A knockdown decreased proliferation of Lewis lung carcinoma cells (LLCs). •Sema3A knockdown decreased mTORC1 levels and glycolytic activity in LLCs. •Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation. •Sema3A promotes shift from oxidative phosphorylation to aerobic glycolysis viamore » mTORC1.« less

Authors:
; ;
Publication Date:
OSTI Identifier:
22598799
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 476; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; CARCINOMAS; CELL PROLIFERATION; GLUCOSE; GLYCOLYSIS; INHIBITION; LUNGS; METASTASES; MICE; OXIDATION; PHOSPHORYLATION

Citation Formats

Yamada, Daisuke, Kawahara, Kohichi, and Maeda, Takehiko, E-mail: maeda@nupals.ac.jp. mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.05.147.
Yamada, Daisuke, Kawahara, Kohichi, & Maeda, Takehiko, E-mail: maeda@nupals.ac.jp. mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling. United States. doi:10.1016/J.BBRC.2016.05.147.
Yamada, Daisuke, Kawahara, Kohichi, and Maeda, Takehiko, E-mail: maeda@nupals.ac.jp. Fri . "mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling". United States. doi:10.1016/J.BBRC.2016.05.147.
@article{osti_22598799,
title = {mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling},
author = {Yamada, Daisuke and Kawahara, Kohichi and Maeda, Takehiko, E-mail: maeda@nupals.ac.jp},
abstractNote = {Aberration of signaling pathways by genetic mutations or alterations in the surrounding tissue environments can result in tumor development or metastasis. However, signaling molecules responsible for these processes have not been completely elucidated. Here, we used mouse Lewis lung carcinoma cells (LLC) to explore the mechanism by which the oncogenic activity of Semaphorin3A (Sema3A) signaling is regulated. Sema3A knockdown by shRNA did not affect apoptosis, but decreased cell proliferation in LLCs; both the mammalian target of rapamycin complex 1 (mTORC1) level and glycolytic activity were also decreased. In addition, Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation by oligomycin, but conferred resistance to decreased cell viability induced by glucose starvation. Furthermore, recombinant SEMA3A rescued the attenuation of cell proliferation and glycolytic activity in LLCs after Sema3A knockdown, whereas mTORC1 inhibition by rapamycin completely counteracted this effect. These results demonstrate that Sema3A signaling exerts its oncogenic effect by promoting an mTORC1-mediated metabolic shift from oxidative phosphorylation to aerobic glycolysis. -- Highlights: •Sema3A knockdown decreased proliferation of Lewis lung carcinoma cells (LLCs). •Sema3A knockdown decreased mTORC1 levels and glycolytic activity in LLCs. •Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation. •Sema3A promotes shift from oxidative phosphorylation to aerobic glycolysis via mTORC1.},
doi = {10.1016/J.BBRC.2016.05.147},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 476,
place = {United States},
year = {Fri Aug 05 00:00:00 EDT 2016},
month = {Fri Aug 05 00:00:00 EDT 2016}
}