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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2018.00376

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

 Yuri Namba1,  Chiharu Sogawa1, Yuka Okusha1, Kisho Ono1, Jun Murakami1, Eriko Aoyama1, Kazumi Ohyama1,  Jun-ichi Asaumi1, Masaharu Takigawa1, Kuniaki Okamoto1,  Stuart K. Calderwood2, Ken-ichi Kozaki1 and  Takanori Eguchi1*
  • 1Okayama University, Japan
  • 2Beth Israel Deaconess Medical Center, Harvard Medical School, United States

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% to 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, 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: ABCG1, Tumoroid, extracellular vesicles, Metastatic cancer, hypoxia

Received: 08 Apr 2018; Accepted: 22 Aug 2018.

Edited by:

Saverio Marchi, University of Ferrara, Italy

Reviewed by:

Saraswati Sukumar, School of Medicine, Johns Hopkins University, United States
Alessandro Rimessi, University of Ferrara, Italy  

Copyright: © 2018 Namba, Sogawa, Okusha, Ono, Murakami, Aoyama, Ohyama, Asaumi, Takigawa, Okamoto, Calderwood, Kozaki and Eguchi. 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.

* Correspondence: Dr. Takanori Eguchi, Okayama University, Okayama, Japan, eguchi.takanori@gmail.com