---
_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'
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  relation: main_file
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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: '12268'
abstract:
- lang: eng
  text: The complexity of the microenvironment effects on cell response, show accumulating
    evidence that glioblastoma (GBM) migration and invasiveness are influenced by
    the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition
    (EMT) is a well-recognized driving force of the invasive behavior of cancer. However,
    the primary mechanisms of EMT initiation and progression remain unclear. We have
    previously showed that certain substrate stiffness can selectively stimulate human
    GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies
    several known EMT mediators to uncover the reason of the regulation and response
    to these stiffnesses. Our results revealed that changing the rigidity of the mechanical
    environment tuned the response of both cell lines through change in morphological
    features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions
    in an interrelated manner. Specifically, a stiffer microenvironment induced a
    mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic
    ROS expression and lower mitochondrial ROS. Finally, we observed that cells more
    motile showed a more depolarized mitochondrial membrane potential. Unravelling
    the process that regulates GBM cells’ infiltrative behavior could provide new
    opportunities for identification of new targets and less invasive approaches for
    treatment.
acknowledgement: "The research leading to these results has received funding from
  AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG
  2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful
  to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia:
  DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia
  e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE
  n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for
  useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela
  Marchetti for practical administrative support."
article_number: '983507'
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Ilaria Elena
  full_name: Palamà, Ilaria Elena
  last_name: Palamà
- first_name: Stefania
  full_name: D’Amone, Stefania
  last_name: D’Amone
- first_name: Clotilde
  full_name: Lauro, Clotilde
  last_name: Lauro
- first_name: Maria
  full_name: Rosito, Maria
  last_name: Rosito
- first_name: Maddalena
  full_name: Grieco, Maddalena
  last_name: Grieco
- first_name: Patrizia
  full_name: Ratano, Patrizia
  last_name: Ratano
- first_name: Federica
  full_name: Cordella, Federica
  last_name: Cordella
- first_name: Caterina
  full_name: Sanchini, Caterina
  last_name: Sanchini
- first_name: Silvia
  full_name: Di Angelantonio, Silvia
  last_name: Di Angelantonio
- first_name: Davide
  full_name: Ragozzino, Davide
  last_name: Ragozzino
- first_name: Mariafrancesca
  full_name: Cascione, Mariafrancesca
  last_name: Cascione
- first_name: Giuseppe
  full_name: Gigli, Giuseppe
  last_name: Gigli
- first_name: Barbara
  full_name: Cortese, Barbara
  last_name: Cortese
citation:
  ama: Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular
    crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma
    cells. <i>Frontiers in Oncology</i>. 2022;12. doi:<a href="https://doi.org/10.3389/fonc.2022.983507">10.3389/fonc.2022.983507</a>
  apa: Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M.,
    … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
    transition mediators of human glioblastoma cells. <i>Frontiers in Oncology</i>.
    Frontiers Media. <a href="https://doi.org/10.3389/fonc.2022.983507">https://doi.org/10.3389/fonc.2022.983507</a>
  chicago: Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro,
    Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect
    on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human
    Glioblastoma Cells.” <i>Frontiers in Oncology</i>. Frontiers Media, 2022. <a href="https://doi.org/10.3389/fonc.2022.983507">https://doi.org/10.3389/fonc.2022.983507</a>.
  ieee: B. Basilico <i>et al.</i>, “Substrate stiffness effect on molecular crosstalk
    of epithelial-mesenchymal transition mediators of human glioblastoma cells,” <i>Frontiers
    in Oncology</i>, vol. 12. Frontiers Media, 2022.
  ista: Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella
    F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B.
    2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
    transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.
  mla: Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk
    of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” <i>Frontiers
    in Oncology</i>, vol. 12, 983507, Frontiers Media, 2022, doi:<a href="https://doi.org/10.3389/fonc.2022.983507">10.3389/fonc.2022.983507</a>.
  short: B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P.
    Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione,
    G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).
date_created: 2023-01-16T10:00:28Z
date_published: 2022-08-25T00:00:00Z
date_updated: 2023-08-04T09:54:16Z
day: '25'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fonc.2022.983507
external_id:
  isi:
  - '000856524900001'
  pmid:
  - '36091138'
file:
- access_level: open_access
  checksum: efc7edf9f626af31853790c5b598a68c
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T10:25:21Z
  date_updated: 2023-01-30T10:25:21Z
  file_id: '12450'
  file_name: 2022_FrontiersOntology_Basilico.pdf
  file_size: 13588502
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T10:25:21Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
keyword:
- Cancer Research
- Oncology
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Oncology
publication_identifier:
  issn:
  - 2234-943X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
  transition mediators of human glioblastoma cells
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'
...