Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells.

Selnø, Anette Teo Hansen; Schlichtner, Stephanie; Yasinska, Inna M.; Sakhnevych, Svetlana S.; Fiedler, Walter; Wellbrock, Jasmin; Klenova, Elena; Pavlova, Ludmila; Gibbs, Bernhard F.; Degen, Martin; Schnyder, Isabelle; Aliu, Nijas; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V. (2020). Transforming growth factor beta type 1 (TGF-β) and hypoxia-inducible factor 1 (HIF-1) transcription complex as master regulators of the immunosuppressive protein galectin-9 expression in human cancer and embryonic cells. Aging, 12(23), pp. 23478-23496. Impact Journals 10.18632/aging.202343

[img]
Preview
Text
Hansen_Seln__et_al_2020.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (3MB) | Preview

Galectin-9 is one of the key proteins employed by a variety of human malignancies to suppress anti-cancer activities of cytotoxic lymphoid cells and thus escape immune surveillance. Human cancer cells in most cases express higher levels of galectin-9 compared to non-transformed cells. However, the biochemical mechanisms underlying this phenomenon remain unclear. Here we report for the first time that in human cancer as well as embryonic cells, the transcription factors hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) are involved in upregulation of transforming growth factor beta 1 (TGF-β1) expression, leading to activation of the transcription factor Smad3 through autocrine action. This process triggers upregulation of galectin-9 expression in both malignant (mainly in breast and colorectal cancer as well as acute myeloid leukaemia (AML)) and embryonic cells. The effect, however, was not observed in mature non-transformed human cells. TGF-β1-activated Smad3 therefore displays differential behaviour in human cancer and embryonic vs non-malignant cells. This study uncovered a self-supporting biochemical mechanism underlying high levels of galectin-9 expression operated by the human cancer and embryonic cells employed in our investigations. Our results suggest the possibility of using the TGF-β1 signalling pathway as a potential highly efficient target for cancer immunotherapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Surgery
04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Orthodontic Research

UniBE Contributor:

Degen, Martin; Schnyder, Isabelle; Berger, Steffen Michael and Fasler-Kan, Elizaveta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1945-4589

Publisher:

Impact Journals

Language:

English

Submitter:

Renate Imhof-Etter

Date Deposited:

22 Dec 2020 09:38

Last Modified:

30 Dec 2020 01:35

Publisher DOI:

10.18632/aging.202343

PubMed ID:

33295886

Uncontrolled Keywords:

HIF-1 TGF-beta galectin-9 immune escape

BORIS DOI:

10.7892/boris.149972

URI:

https://boris.unibe.ch/id/eprint/149972

Actions (login required)

Edit item Edit item
Provide Feedback