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Osteopontin (OPN/SPP1), a Mediator of Tumor Progression, Is Regulated by the Mesenchymal Transcription Factor Slug/SNAI2 in Colorectal Cancer (CRC)

Abstract : In colorectal cancer (CRC), disease-related death is closely linked to tumor aggressiveness and metastasis. Gene expression profiling of patient tumors has suggested that a more mesenchymal phenotype, present in about one-fourth of all patients, is associated with increased aggressiveness. Accordingly, the mesenchymal transcription factor Slug/SNAI2 has been associated with decreased disease-free survival. To decipher the basis for the Slug-mediated phenotype, we conducted RNAseq experiments with a panel of HT-29 CRC cells expressing different levels of Slug, both in vitro and in tumor models. The results show that osteopontin, a secreted pleotropic protein involved in multiple steps of colorectal cancer progression, was highly upregulated by Slug in vitro, as well as in vivo. We further show that Slug is a direct regulator of osteopontin at the promoter level. The levels of secreted osteopontin were correlated with Slug expression, thereby linking the tumor phenotype to a biomarker available by liquid biopsies. The results also suggest that osteopontin neutralization may attenuate at least some of the Slug-mediated functions.
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https://hal-cnrs.archives-ouvertes.fr/hal-03867389
Contributor : Michèle Sabbah Connect in order to contact the contributor
Submitted on : Wednesday, November 23, 2022 - 12:26:35 PM
Last modification on : Thursday, November 24, 2022 - 3:15:25 AM

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Katyana Amilca-Seba, Tuan Zea Tan, Jean-Paul Thiery, Lila Louadj, Sandrine Thouroude, et al.. Osteopontin (OPN/SPP1), a Mediator of Tumor Progression, Is Regulated by the Mesenchymal Transcription Factor Slug/SNAI2 in Colorectal Cancer (CRC). Cells, 2022, 11 (11), pp.1808. ⟨10.3390/cells11111808⟩. ⟨hal-03867389⟩

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