---
_id: '10712'
abstract:
- lang: eng
  text: Solute carriers are increasingly recognized as participating in a plethora
    of pathologies, including cancer. We describe here the involvement of the orphan
    solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1
    enabled higher levels of metastasis in a mouse model. We identified an increased
    migratory potential in MFSD1-/- tumor cells which was mediated by increased focal
    adhesion turn-over, reduced stability of mature inactive β1 integrin, and the
    resulting increased integrin activation index. We show that MFSD1 promoted recycling
    to the cell surface of endocytosed inactive β1 integrin and thereby protected
    β1 integrin from proteolytic degradation; this led to dampening of the integrin
    activation index. Furthermore, down-regulation of MFSD1 expression was observed
    during early steps of tumorigenesis and higher MFSD1 expression levels correlate
    with a better cancer patient prognosis. In sum, we describe a requirement for
    endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.
acknowledged_ssus:
- _id: Bio
acknowledgement: We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and
  the BioImaging Facility at IST Austria for technical support and assistance. We
  thank the Siekhaus Lab for the careful review of the manuscript and their input.
  MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and
  IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1).
article_number: '777634'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Julia
  full_name: Bicher, Julia
  id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
  last_name: Bicher
- first_name: Merel
  full_name: van Gogh, Merel
  last_name: van Gogh
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Rita
  full_name: Seeböck, Rita
  last_name: Seeböck
- first_name: Bozena
  full_name: Szulc, Bozena
  last_name: Szulc
- first_name: Markus
  full_name: Damme, Markus
  last_name: Damme
- first_name: Mariusz
  full_name: Olczak, Mariusz
  last_name: Olczak
- first_name: Lubor
  full_name: Borsig, Lubor
  last_name: Borsig
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
citation:
  ama: Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1
    integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>.
    2022;12. doi:<a href="https://doi.org/10.3389/fonc.2022.777634">10.3389/fonc.2022.777634</a>
  apa: Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., …
    Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation
    status and thus tumor metastasis. <i>Frontiers in Oncology</i>. Frontiers. <a
    href="https://doi.org/10.3389/fonc.2022.777634">https://doi.org/10.3389/fonc.2022.777634</a>
  chicago: Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck,
    Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus.
    “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor
    Metastasis.” <i>Frontiers in Oncology</i>. Frontiers, 2022. <a href="https://doi.org/10.3389/fonc.2022.777634">https://doi.org/10.3389/fonc.2022.777634</a>.
  ieee: M. Roblek <i>et al.</i>, “The solute carrier MFSD1 decreases β1 integrin’s
    activation status and thus tumor metastasis,” <i>Frontiers in Oncology</i>, vol.
    12. Frontiers, 2022.
  ista: Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak
    M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s
    activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634.
  mla: Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation
    Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>, vol. 12, 777634,
    Frontiers, 2022, doi:<a href="https://doi.org/10.3389/fonc.2022.777634">10.3389/fonc.2022.777634</a>.
  short: M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme,
    M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022).
date_created: 2022-02-01T10:33:50Z
date_published: 2022-02-08T00:00:00Z
date_updated: 2023-08-02T14:05:44Z
day: '08'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.3389/fonc.2022.777634
external_id:
  isi:
  - '000760618800001'
file:
- access_level: open_access
  checksum: 63dfecf30c5bbf9408b3512bd603f78c
  content_type: application/pdf
  creator: cchlebak
  date_created: 2022-02-08T13:26:40Z
  date_updated: 2022-02-08T13:26:40Z
  file_id: '10751'
  file_name: 2022_FrontiersOncol_Roblek.pdf
  file_size: 6303227
  relation: main_file
  success: 1
file_date_updated: 2022-02-08T13:26:40Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 2637E9C0-B435-11E9-9278-68D0E5697425
  grant_number: 'LSC16-021 '
  name: Investigating the role of the novel major superfamily facilitator transporter
    family member MFSD1 in metastasis
publication: Frontiers in Oncology
publication_identifier:
  issn:
  - 2234-943X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: confirmation
    url: https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/
scopus_import: '1'
status: public
title: The solute carrier MFSD1 decreases β1 integrin’s activation status and thus
  tumor metastasis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2022'
...
---
_id: '544'
abstract:
- lang: eng
  text: Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes,
    are essential for immune responses, but also play key roles from early development
    to death through their interactions with other cell types. They regulate homeostasis
    and signaling during development, stem cell proliferation, metabolism, cancer,
    wound responses and aging, displaying intriguing molecular and functional conservation
    with vertebrate macrophages. Given the relative ease of genetics in Drosophila
    compared to vertebrates, tools permitting visualization and genetic manipulation
    of plasmatocytes and surrounding tissues independently at all stages would greatly
    aid in fully understanding these processes, but are lacking. Here we describe
    a comprehensive set of transgenic lines that allow this. These include extremely
    brightly fluorescing mCherry-based lines that allow GAL4-independent visualization
    of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8
    through adulthood in both live and fixed samples even as heterozygotes, greatly
    facilitating screening. These lines allow live visualization and tracking of embryonic
    plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing
    with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes
    and inner tissues can be seen in live or fixed embryos, larvae and adults. They
    permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout
    life. To facilitate genetic analysis of reciprocal signaling, we have also made
    a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers
    allows independent genetic manipulation of both plasmatocytes and surrounding
    tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes,
    both of which function from the early embryo to the adult.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: ' A. Ratheesh also by Marie Curie IIF GA-2012-32950BB:DICJI, Marko
  Roblek by the provincial government of Lower Austria, K. Valoskova and S. Wachner
  by DOC Fellowships from the Austrian Academy of Sciences, '
article_processing_charge: No
author:
- first_name: Attila
  full_name: György, Attila
  id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
  last_name: György
  orcid: 0000-0002-1819-198X
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Aparna
  full_name: Ratheesh, Aparna
  id: 2F064CFE-F248-11E8-B48F-1D18A9856A87
  last_name: Ratheesh
  orcid: 0000-0001-7190-0776
- first_name: Katarina
  full_name: Valosková, Katarina
  id: 46F146FC-F248-11E8-B48F-1D18A9856A87
  last_name: Valosková
- first_name: Vera
  full_name: Belyaeva, Vera
  id: 47F080FE-F248-11E8-B48F-1D18A9856A87
  last_name: Belyaeva
- first_name: Stephanie
  full_name: Wachner, Stephanie
  id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
  last_name: Wachner
- first_name: Yutaka
  full_name: Matsubayashi, Yutaka
  last_name: Matsubayashi
- first_name: Besaiz
  full_name: Sanchez Sanchez, Besaiz
  last_name: Sanchez Sanchez
- first_name: Brian
  full_name: Stramer, Brian
  last_name: Stramer
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
citation:
  ama: 'György A, Roblek M, Ratheesh A, et al. Tools allowing independent visualization
    and genetic manipulation of Drosophila melanogaster macrophages and surrounding
    tissues. <i>G3: Genes, Genomes, Genetics</i>. 2018;8(3):845-857. doi:<a href="https://doi.org/10.1534/g3.117.300452">10.1534/g3.117.300452</a>'
  apa: 'György, A., Roblek, M., Ratheesh, A., Valosková, K., Belyaeva, V., Wachner,
    S., … Siekhaus, D. E. (2018). Tools allowing independent visualization and genetic
    manipulation of Drosophila melanogaster macrophages and surrounding tissues. <i>G3:
    Genes, Genomes, Genetics</i>. Genetics Society of America. <a href="https://doi.org/10.1534/g3.117.300452">https://doi.org/10.1534/g3.117.300452</a>'
  chicago: 'György, Attila, Marko Roblek, Aparna Ratheesh, Katarina Valosková, Vera
    Belyaeva, Stephanie Wachner, Yutaka Matsubayashi, Besaiz Sanchez Sanchez, Brian
    Stramer, and Daria E Siekhaus. “Tools Allowing Independent Visualization and Genetic
    Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.”
    <i>G3: Genes, Genomes, Genetics</i>. Genetics Society of America, 2018. <a href="https://doi.org/10.1534/g3.117.300452">https://doi.org/10.1534/g3.117.300452</a>.'
  ieee: 'A. György <i>et al.</i>, “Tools allowing independent visualization and genetic
    manipulation of Drosophila melanogaster macrophages and surrounding tissues,”
    <i>G3: Genes, Genomes, Genetics</i>, vol. 8, no. 3. Genetics Society of America,
    pp. 845–857, 2018.'
  ista: 'György A, Roblek M, Ratheesh A, Valosková K, Belyaeva V, Wachner S, Matsubayashi
    Y, Sanchez Sanchez B, Stramer B, Siekhaus DE. 2018. Tools allowing independent
    visualization and genetic manipulation of Drosophila melanogaster macrophages
    and surrounding tissues. G3: Genes, Genomes, Genetics. 8(3), 845–857.'
  mla: 'György, Attila, et al. “Tools Allowing Independent Visualization and Genetic
    Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.”
    <i>G3: Genes, Genomes, Genetics</i>, vol. 8, no. 3, Genetics Society of America,
    2018, pp. 845–57, doi:<a href="https://doi.org/10.1534/g3.117.300452">10.1534/g3.117.300452</a>.'
  short: 'A. György, M. Roblek, A. Ratheesh, K. Valosková, V. Belyaeva, S. Wachner,
    Y. Matsubayashi, B. Sanchez Sanchez, B. Stramer, D.E. Siekhaus, G3: Genes, Genomes,
    Genetics 8 (2018) 845–857.'
date_created: 2018-12-11T11:47:05Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2024-03-25T23:30:15Z
day: '01'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.1534/g3.117.300452
ec_funded: 1
external_id:
  isi:
  - '000426693300011'
file:
- access_level: open_access
  checksum: 7d9d28b915159078a4ca7add568010e8
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:11:48Z
  date_updated: 2020-07-14T12:46:56Z
  file_id: '4905'
  file_name: IST-2018-990-v1+1_2018_Gyoergy_Tools_allowing.pdf
  file_size: 2251222
  relation: main_file
file_date_updated: 2020-07-14T12:46:56Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 845 - 857
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: Drosophila TNFa´s Funktion in Immunzellen
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29638
  name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 2637E9C0-B435-11E9-9278-68D0E5697425
  grant_number: 'LSC16-021 '
  name: Investigating the role of the novel major superfamily facilitator transporter
    family member MFSD1 in metastasis
- _id: 2536F660-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '334077'
  name: Investigating the role of transporters in invasive migration through junctions
publication: 'G3: Genes, Genomes, Genetics'
publication_status: published
publisher: Genetics Society of America
publist_id: '7271'
pubrep_id: '990'
quality_controlled: '1'
related_material:
  record:
  - id: '6530'
    relation: research_paper
  - id: '6543'
    relation: research_paper
  - id: '11193'
    relation: dissertation_contains
    status: public
  - id: '6546'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Tools allowing independent visualization and genetic manipulation of Drosophila
  melanogaster macrophages and surrounding tissues
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 8
year: '2018'
...