Počet záznamů: 1
TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial-Mesenchymal Transition and Invasiveness
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SYSNO ASEP 0561378 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial-Mesenchymal Transition and Invasiveness Tvůrce(i) Švec, Jiří (UMG-J) RID
Šťastná, Monika (UMG-J)
Janečková, Lucie (UMG-J)
Hrčkulák, Dušan (UMG-J)
Vojtěchová, Martina (UMG-J) RID
Onhajzer, Jakub (UMG-J)
Kříž, Vítězslav (UMG-J)
Galušková, Kateřina (UMG-J)
Šloncová, Eva (UMG-J)
Kubovčiak, Jan (UMG-J)
Pfeiferová, Lucie (UMG-J)
Hrudka, J. (CZ)
Matěj, R. (CZ)
Waldauf, P. (CZ)
Havluj, L. (CZ)
Kolář, Michal (UMG-J) RID, ORCID
Kořínek, Vladimír (UMG-J) RIDCelkový počet autorů 17 Číslo článku 4137 Zdroj.dok. Cancers (Basel). - : MDPI
Roč. 14, č. 17 (2022)Poč.str. 35 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova apc ; colorectal cancer ; emt ; expression profiling ; organoids ; tacstd2 ; WNT/beta-catenin signaling Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Oncology CEP GA18-26324S GA ČR - Grantová agentura ČR LX22NPO5102 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LM2018129 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF16_019/0000785 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000852560200001 DOI 10.3390/cancers14174137 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2023 Elektronická adresa https://doi.org/10.3390/cancers14174137
Počet záznamů: 1