TROP2 represents a negative prognostic factor in colorectal adenocarcinoma and its expression is associated with features of epithelial-mesenchymal transition and invasiveness

Švec, Jiří; Šťastná, Monika; Janečková, Lucie; Hrčkulák, Dušan; Vojtěchová, Martina; Onhajzer, Jakub; Křı́ž, Vı́tězslav; Galušková, Kateřina; Šloncová, Eva; Kubovčiak, Jan; Pfeiferová, Lucie; Hrudka, Jan; Matěj, Radoslav; Waldauf, Petr; Havlůj, Lukáš; Kolář, Michal; Kor̆ínek, Vladimír

doi:10.1101/2022.07.27.501720

Cited by 1 publication

(1 citation statement)

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“…Trop2 has shown identical characteristics to EpCAM in virtually all features examined so far, including structure and biochemical interactions (Fagotto, 2020a; Fagotto and Aslemarz, 2020). Trop2 has been also linked to cancer, but, again, its actual role remains to be established (Fagotto and Aslemarz, 2020; Lenárt et al, 2020; Švec et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

An EpCAM/Trop2 mechanostat differentially regulates collective behaviour of human carcinoma cells

Aslemarz

Fagotto-Kaufmann

Ruppel

et al. 2022

Preprint

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EpCAM is well known as a carcinoma associated cell surface protein that is widely used as an epithelial cancer biomarker. Despite its clear link to cancer development, whether it plays an actual role in cancer metastasis remains unclear. It is known, however, to downregulate myosin contractility, a key parameter involved in cell adhesion and migration. We have examined here the potential morphogenetic impact of the high EpCAM expression that characterizes epithelial breast cancer cells, using spheroids of MCF7 cells as model of pre-metastatic cells. We found that EpCAM acted as a repressor of collective migration, while it stimulated single cell migration. Using a combination of cell biological and biophysical approaches, we show that EpCAM depletion globally increased cell contractility, in such a way that the resulting balance of tensions was favorable to cell adhesiveness, resulting in increased tissue cohesion and switch toward collective migration. Most epithelial cells, including MCF7 cells, also express Trop2, a close relative of EpCAM. Intriguingly, we found that Trop2 depletion led to the exact opposite global phenotype from EpCAM depletion, stimulating single cell migration, while decreasing tissue cohesiveness and collective migration. Comparison with EpCAM showed that while both proteins contributed to moderate cell contractility, they differentially modulate the balance of cortical myosin contractility between free edges and adhesive contacts. These differences appeared to rely on subtle differences in the distribution of these two surface proteins. These results highlight the crucial importance of a fine balance of myosin contractility downstream of EpCAM and Trop2, which act as a mechanostat in controlling tissue cohesiveness and in stimulating distinct modes of migration.

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