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

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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)

Content Provider	MDPI
Author	Amilca-Seba, Katyana Tan, Tuan Zea Thiery, Jean-Paul Louadj, Lila Thouroude, Sandrine Bouygues, Anaïs Sabbah, Michèle Larsen, Annette K. Denis, Jérôme A.
Copyright Year	2022
Description	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.
Starting Page	1808
e-ISSN	20734409
DOI	10.3390/cells11111808
Journal	Cells
Issue Number	11
Volume Number	11
Language	English
Publisher	MDPI
Publisher Date	2022-05-31
Access Restriction	Open
Subject Keyword	Cells Oncology Colorectal Cancer (crc) Epithelial–mesenchymal Transition (emt) Slug/snai2 Transcription Factor Osteopontin (opn/spp1)
Content Type	Text
Resource Type	Article

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