TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial-Mesenchymal Transition and Invasiveness

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00561378" target="_blank" >RIV/68378050:_____/22:00561378 - isvavai.cz</a>

Alternative codes found

RIV/00064173:_____/22:43923826 RIV/00216208:11120/22:43923826 RIV/00064190:_____/22:N0000038

Result on the web

<a href="https://doi.org/10.3390/cancers14174137" target="_blank" >https://doi.org/10.3390/cancers14174137</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers14174137" target="_blank" >10.3390/cancers14174137</a>

Result language

angličtina

Original language name

TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial-Mesenchymal Transition and Invasiveness

Original language description

Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with a poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 is expressed in preneoplastic lesions, and its expression is maintained in most colorectal cancers (CRC). High TROP2 positivity correlated with lymph node metastases and poor tumor differentiation and was a negative prognostic factor. To investigate the role of TROP2 in intestinal tumors, we analyzed two mouse models with conditional disruption of the adenomatous polyposis coli (Apc) tumor-suppressor gene, human adenocarcinoma samples, patient-derived organoids, and TROP2-deficient tumor cells. We found that Trop2 is produced early after Apc inactivation and its expression is associated with the transcription of genes involved in epithelial-mesenchymal transition, the regulation of migration, invasiveness, and extracellular matrix remodeling. A functionally similar group of genes was also enriched in TROP2-positive cells from human CRC samples. To decipher the driving mechanism of TROP2 expression, we analyzed its promoter. In human cells, this promoter was activated by beta-catenin and additionally by the Yes1-associated transcriptional regulator (YAP). The regulation of TROP2 expression by active YAP was verified by YAP knockdown in CRC cells. Our results suggest a possible link between aberrantly activated Wnt/beta-catenin signaling, YAP, and TROP2 expression.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

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

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers (Basel)

ISSN

2072-6694

e-ISSN

2072-6694

Volume of the periodical

14

Issue of the periodical within the volume

17

Country of publishing house

CH - SWITZERLAND

Number of pages

35

Pages from-to

4137

UT code for WoS article

000852560200001

EID of the result in the Scopus database

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