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Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells

The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. C...

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Autores principales: Namba, Yuri, Sogawa, Chiharu, Okusha, Yuka, Kawai, Hotaka, Itagaki, Mami, Ono, Kisho, Murakami, Jun, Aoyama, Eriko, Ohyama, Kazumi, Asaumi, Jun-ichi, Takigawa, Masaharu, Okamoto, Kuniaki, Calderwood, Stuart K., Kozaki, Ken-ichi, Eguchi, Takanori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191470/
https://www.ncbi.nlm.nih.gov/pubmed/30364132
http://dx.doi.org/10.3389/fonc.2018.00376
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author Namba, Yuri
Sogawa, Chiharu
Okusha, Yuka
Kawai, Hotaka
Itagaki, Mami
Ono, Kisho
Murakami, Jun
Aoyama, Eriko
Ohyama, Kazumi
Asaumi, Jun-ichi
Takigawa, Masaharu
Okamoto, Kuniaki
Calderwood, Stuart K.
Kozaki, Ken-ichi
Eguchi, Takanori
author_facet Namba, Yuri
Sogawa, Chiharu
Okusha, Yuka
Kawai, Hotaka
Itagaki, Mami
Ono, Kisho
Murakami, Jun
Aoyama, Eriko
Ohyama, Kazumi
Asaumi, Jun-ichi
Takigawa, Masaharu
Okamoto, Kuniaki
Calderwood, Stuart K.
Kozaki, Ken-ichi
Eguchi, Takanori
author_sort Namba, Yuri
collection PubMed
description The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10–35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.
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spelling pubmed-61914702018-10-24 Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells Namba, Yuri Sogawa, Chiharu Okusha, Yuka Kawai, Hotaka Itagaki, Mami Ono, Kisho Murakami, Jun Aoyama, Eriko Ohyama, Kazumi Asaumi, Jun-ichi Takigawa, Masaharu Okamoto, Kuniaki Calderwood, Stuart K. Kozaki, Ken-ichi Eguchi, Takanori Front Oncol Oncology The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10–35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo. Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression. Frontiers Media S.A. 2018-10-10 /pmc/articles/PMC6191470/ /pubmed/30364132 http://dx.doi.org/10.3389/fonc.2018.00376 Text en Copyright © 2018 Namba, Sogawa, Okusha, Kawai, Itagaki, Ono, Murakami, Aoyama, Ohyama, Asaumi, Takigawa, Okamoto, Calderwood, Kozaki and Eguchi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Namba, Yuri
Sogawa, Chiharu
Okusha, Yuka
Kawai, Hotaka
Itagaki, Mami
Ono, Kisho
Murakami, Jun
Aoyama, Eriko
Ohyama, Kazumi
Asaumi, Jun-ichi
Takigawa, Masaharu
Okamoto, Kuniaki
Calderwood, Stuart K.
Kozaki, Ken-ichi
Eguchi, Takanori
Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells
title Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells
title_full Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells
title_fullStr Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells
title_full_unstemmed Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells
title_short Depletion of Lipid Efflux Pump ABCG1 Triggers the Intracellular Accumulation of Extracellular Vesicles and Reduces Aggregation and Tumorigenesis of Metastatic Cancer Cells
title_sort depletion of lipid efflux pump abcg1 triggers the intracellular accumulation of extracellular vesicles and reduces aggregation and tumorigenesis of metastatic cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191470/
https://www.ncbi.nlm.nih.gov/pubmed/30364132
http://dx.doi.org/10.3389/fonc.2018.00376
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