ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2

• DOI: 10.1007/s00018-022-04445-5
• Publication Date: 2022-07-15T04:02:56Z
• Authors: Kerstin Huebner; Katharina Erlenba...; Jan Prochazka; Ilir Sheraj; Chuanpit Hampel; Blanka Mrazkova; Tereza Michalcikova; Jolana Tureckova; Veronika Iatsiuk; Anne Weissmann; Fulvia Ferrazzi; Philipp Kunze; Enise Nalli; Elisabeth Sammer; Annemarie Gehring; Marie M. Cheema; Markus Eckstein; Eva-Maria Paap; Agnes Soederberg; Corinna Fischer; Sushmita Paul; Vijayalakshmi Mah...; Benardina Ndreshk...; Melanie A. Meier; Susanne Muehlich; Carol I. Geppert; Susanne Merkel; Robert Grutzmann; Adriana Roehe; Sreeparna Banerjee; Arndt Hartmann; Radislav Sedlacek; Regine Schneider-...
• Keywords: Adherens junction

In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due only limited studies, significance of ATF2 colorectal cancer (CRC) is not well understood. We report that low levels correlated with worse prognosis and tumor aggressiveness CRC patients. NanoString gene expression ChIP analysis confirmed trophoblast cell surface antigen (TROP2) as a novel inhibitory target gene. This inverse correlation was further observed primary human tissues. Immunostainings revealed high intratumoral heterogeneity for TROP2 sustained also liver metastasis. Mechanistically, our vitro data CRISPR/Cas9-generated knockout (KO) clones were critical de-adhesion increased migration without triggering EMT. enriched filopodia displaced Paxillin from adherens junctions. vivo imaging, micro-computer tomography, immunostainings verified an ATF2KO/TROP2high status triggered invasiveness mouse chicken xenograft models. silico provided direct support ATF2low/TROP2high defined high-risk Finally, demonstrate acts suppressor by inhibiting driver TROP2. Therapeutic targeting might prevent particularly first steps metastasis, i.e., invasion colon cells.