Autophagy-dependent regulation of tumor metastasis by myeloid cells

Masahisa Jinushi, Tomoko Morita, Zhihang Xu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Hideo Yagita, Yutaka Kawakami

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Autophagy is a vital process controlling the lysosomal degradation of cellular organelles and thereby regulating tissue homeostasis in an environment-dependent fashion. Recent studies have unveiled the critical role of tumor cell-derived autophagy in regulating pro-tumor and anti-tumor processes depending on different stages and tumor microenvironments. However, the precise mechanism whereby autophagy regulates tumor progression remains largely unclear. Since myeloid cells contribute to tumor progression and metastasis, we evaluated the role of myeloid cell-specific autophagy in the regulation of tumor progression. We found that the number and size of metastatic lesions were smaller in myeloid cell-specific autophagy-deficient mice. Furthermore, autophagy-mediated regulation of TGF-β in myeloid cells was associated with the induction of epithelial-mesenchymal transition (EMT), which increases the invasive and metastatic potentials of tumor cells. Myeloid-derived autophagy also plays a critical role in impairing antitumor immune responses and promoting the survival and accumulation of M2 macrophages in tumor tissues in a CSF-1 and TGF-β-dependent manner. Taken together, our findings elucidate previously unrecognized mechanisms by which myeloid cells promote tumor progression through autophagy-mediated regulation of malignancy and immune tolerance.

Original languageEnglish
Article numbere0179357
JournalPLoS One
Volume12
Issue number7
DOIs
Publication statusPublished - 2017 Jul 1

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autophagy
Autophagy
Myeloid Cells
metastasis
Tumors
Neoplasm Metastasis
neoplasms
Neoplasms
cells
Tissue homeostasis
Cells
immunosuppression
Immune Tolerance
Macrophage Colony-Stimulating Factor
Epithelial-Mesenchymal Transition
Tumor Microenvironment
Macrophages
organelles
homeostasis
macrophages

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Jinushi, M., Morita, T., Xu, Z., Kinoshita, I., Dosaka-Akita, H., Yagita, H., & Kawakami, Y. (2017). Autophagy-dependent regulation of tumor metastasis by myeloid cells. PLoS One, 12(7), [e0179357]. https://doi.org/10.1371/journal.pone.0179357

Autophagy-dependent regulation of tumor metastasis by myeloid cells. / Jinushi, Masahisa; Morita, Tomoko; Xu, Zhihang; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Yagita, Hideo; Kawakami, Yutaka.

In: PLoS One, Vol. 12, No. 7, e0179357, 01.07.2017.

Research output: Contribution to journalArticle

Jinushi, M, Morita, T, Xu, Z, Kinoshita, I, Dosaka-Akita, H, Yagita, H & Kawakami, Y 2017, 'Autophagy-dependent regulation of tumor metastasis by myeloid cells', PLoS One, vol. 12, no. 7, e0179357. https://doi.org/10.1371/journal.pone.0179357
Jinushi M, Morita T, Xu Z, Kinoshita I, Dosaka-Akita H, Yagita H et al. Autophagy-dependent regulation of tumor metastasis by myeloid cells. PLoS One. 2017 Jul 1;12(7). e0179357. https://doi.org/10.1371/journal.pone.0179357
Jinushi, Masahisa ; Morita, Tomoko ; Xu, Zhihang ; Kinoshita, Ichiro ; Dosaka-Akita, Hirotoshi ; Yagita, Hideo ; Kawakami, Yutaka. / Autophagy-dependent regulation of tumor metastasis by myeloid cells. In: PLoS One. 2017 ; Vol. 12, No. 7.
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