Depletion of lipid efflux pump ABCG1 triggers the intracellular accumulation of extracellular vesicles and reduces aggregation and tumorigenesis of metastatic cancer cells

Yuri Namba, Chiharu Sogawa, Yuka Okusya, Hotaka Kawai, Mami Itagaki, Kisho Ono, Jun Murakami, Eriko Aoyama, Kazumi Ohyama, Jun-Ichi Asaumi, Masaharu Takigawa, Kuniaki Okamoto, Stuart K. Calderwood, Ken ichi Kozaki, Takanori Eguchi

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2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number376
JournalFrontiers in Oncology
Volume8
Issue numberOCT
DOIs
Publication statusPublished - Oct 10 2018

Fingerprint

ATP-Binding Cassette Transporters
Carcinogenesis
Lipids
Neoplasms
Organoids
Extracellular Vesicles
Hypoxia-Inducible Factor 1
Poisons
Growth
Colonic Neoplasms
Cholesterol

Keywords

  • ABCG transporter
  • ABCG1
  • Extracellular vesicle
  • Hypoxia
  • Metastatic cancer
  • Tumoroids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Depletion of lipid efflux pump ABCG1 triggers the intracellular accumulation of extracellular vesicles and reduces aggregation and tumorigenesis of metastatic cancer cells",
abstract = "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.",
keywords = "ABCG transporter, ABCG1, Extracellular vesicle, Hypoxia, Metastatic cancer, Tumoroids",
author = "Yuri Namba and Chiharu Sogawa and Yuka Okusya and Hotaka Kawai and Mami Itagaki and Kisho Ono and Jun Murakami and Eriko Aoyama and Kazumi Ohyama and Jun-Ichi Asaumi and Masaharu Takigawa and Kuniaki Okamoto and Calderwood, {Stuart K.} and Kozaki, {Ken ichi} and Takanori Eguchi",
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T1 - Depletion of lipid efflux pump ABCG1 triggers the intracellular accumulation of extracellular vesicles and reduces aggregation and tumorigenesis of metastatic cancer cells

AU - Namba, Yuri

AU - Sogawa, Chiharu

AU - Okusya, Yuka

AU - Kawai, Hotaka

AU - Itagaki, Mami

AU - Ono, Kisho

AU - Murakami, Jun

AU - Aoyama, Eriko

AU - Ohyama, Kazumi

AU - Asaumi, Jun-Ichi

AU - Takigawa, Masaharu

AU - Okamoto, Kuniaki

AU - Calderwood, Stuart K.

AU - Kozaki, Ken ichi

AU - Eguchi, Takanori

PY - 2018/10/10

Y1 - 2018/10/10

N2 - 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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KW - Hypoxia

KW - Metastatic cancer

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