ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00559440" target="_blank" >RIV/68378050:_____/22:00559440 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00018-022-04445-5" target="_blank" >https://link.springer.com/article/10.1007/s00018-022-04445-5</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-022-04445-5" target="_blank" >10.1007/s00018-022-04445-5</a>
Alternative languages
Result language
angličtina
Original language name
ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2
Original language description
In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues. Immunostainings revealed that high intratumoral heterogeneity for ATF2 and TROP2 expression was sustained also in liver metastasis. Mechanistically, our in vitro data of CRISPR/Cas9-generated ATF2 knockout (KO) clones revealed that high TROP2 levels were critical for cell de-adhesion and increased cell migration without triggering EMT. TROP2 was enriched in filopodia and displaced Paxillin from adherens junctions. In vivo imaging, micro-computer tomography, and immunostainings verified that an ATF2(KO)/TROP2(high) status triggered tumor invasiveness in in vivo mouse and chicken xenograft models. In silico analysis provided direct support that ATF2(low)/TROP2(high) expression status defined high-risk CRC patients. Finally, our data demonstrate that ATF2 acts as a tumor suppressor by inhibiting the cancer driver TROP2. Therapeutic TROP2 targeting might prevent particularly the first steps in metastasis, i.e., the de-adhesion and invasion of colon cancer cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and Molecular Life Sciences
ISSN
1420-682X
e-ISSN
1420-9071
Volume of the periodical
79
Issue of the periodical within the volume
8
Country of publishing house
CH - SWITZERLAND
Number of pages
17
Pages from-to
423
UT code for WoS article
000826018000001
EID of the result in the Scopus database
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