Tgf-β1 transcriptionally promotes 90K expression: possible implications for cancer progression.


Journal

Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035

Informations de publication

Date de publication:
22 Apr 2021
Historique:
received: 11 10 2020
accepted: 18 03 2021
revised: 21 02 2021
entrez: 23 4 2021
pubmed: 24 4 2021
medline: 24 4 2021
Statut: epublish

Résumé

The 90K protein, also known as Mac-2 BP or LGALS3BP, can activate the immune response in part by increasing major histocompatibility (MHC) class I levels. In studies on a non-immune cell model, the rat FRTL-5 cell line, we observed that transforming growth factor (TGF)-β1, like γ-interferon (IFN), increased 90K levels, despite its immunosuppressive functions and the ability to decrease MHC class I. To explain this paradoxical result, we investigated the mechanisms involved in the TGF-β1 regulation of 90K expression with the aim to demonstrate that TGF-β1 utilizes different molecular pathways to regulate the two genes. We found that TGF-β1 was able to increase the binding of Upstream Stimulatory Factors, USF1 and USF2, to an E-box element, CANNTG, at -1926 to -1921 bp, upstream of the interferon response element (IRE) in the 90K promoter. Thyrotropin (TSH) suppressed constitutive and γ-IFN-induced 90K expression by decreasing USF binding to the E-box. TGF-β1 was able to overcome TSH suppression at the transcriptional level by increasing USF binding to the E-box. We suggest that the ability of TGF-β1 to increase 90K did not result in an increase in MHC class I because of a separate suppressive action of TGF-β1 directly on the MHC class I gene. We propose that the increased levels of 90K may play a role, rather than in immune response, in the context of the TGF-β1-induced changing of the cellular microenvironment that predisposes to cell motility and cancer progression. Consistently, analyzing the publicly available cancer patient data sets cBioPortal, we found that 90K expression directly correlated with TGF-β1 and USFs and that high levels of 90K were significantly associated with increased mortality in patients affected by different types of cancer.

Identifiants

pubmed: 33888686
doi: 10.1038/s41420-021-00469-1
pii: 10.1038/s41420-021-00469-1
pmc: PMC8062489
doi:

Types de publication

Journal Article

Langues

eng

Pagination

86

Commentaires et corrections

Type : ErratumIn

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Auteurs

Antonino Grassadonia (A)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy. grassadonia@unich.it.

Vincenzo Graziano (V)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.

Sara Pagotto (S)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Angelo Veronese (A)

Department of Medicine and Ageing Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Cesidio Giuliani (C)

Department of Medicine and Ageing Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Marco Marchisio (M)

Department of Medicine and Ageing Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Paola Lanuti (P)

Department of Medicine and Ageing Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Michele De Tursi (M)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Maurizia D'Egidio (M)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Pietro Di Marino (P)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Davide Brocco (D)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Patrizia Vici (P)

Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Laura De Lellis (L)

Department of Pharmacy and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Alessandro Cama (A)

Department of Pharmacy and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Clara Natoli (C)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Nicola Tinari (N)

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

Classifications MeSH