Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL

Research output: Contribution to journal › Journal article › Research › peer-review

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Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL. / Chi, Cheng; Harth, Lisa; Galera, Marina Ramírez; Torrealba, Marina Passos; Vadivel, Chella Krishna; Geisler, Carsten; Bonefeld, Charlotte Menné; Nielsen, Pia Rude; Bzorek, Michael; Becker, Jürgen C.; Gjerdrum, Lise Mette Rahbek; Ødum, Niels; Woetmann, Anders.

In: Cancers, Vol. 14, No. 18, 4491, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chi, C, Harth, L, Galera, MR, Torrealba, MP, Vadivel, CK, Geisler, C, Bonefeld, CM, Nielsen, PR, Bzorek, M, Becker, JC, Gjerdrum, LMR, Ødum, N & Woetmann, A 2022, 'Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL', Cancers, vol. 14, no. 18, 4491. https://doi.org/10.3390/cancers14184491

APA

Chi, C., Harth, L., Galera, M. R., Torrealba, M. P., Vadivel, C. K., Geisler, C., Bonefeld, C. M., Nielsen, P. R., Bzorek, M., Becker, J. C., Gjerdrum, L. M. R., Ødum, N., & Woetmann, A. (2022). Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL. Cancers, 14(18), [4491]. https://doi.org/10.3390/cancers14184491

Vancouver

Chi C, Harth L, Galera MR, Torrealba MP, Vadivel CK, Geisler C et al. Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL. Cancers. 2022;14(18). 4491. https://doi.org/10.3390/cancers14184491

Author

Chi, Cheng ; Harth, Lisa ; Galera, Marina Ramírez ; Torrealba, Marina Passos ; Vadivel, Chella Krishna ; Geisler, Carsten ; Bonefeld, Charlotte Menné ; Nielsen, Pia Rude ; Bzorek, Michael ; Becker, Jürgen C. ; Gjerdrum, Lise Mette Rahbek ; Ødum, Niels ; Woetmann, Anders. / Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL. In: Cancers. 2022 ; Vol. 14, No. 18.

Bibtex

@article{6d1d3b86a3da439083f34d140743f3bf,
title = "Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL",
abstract = "Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin{\textquoteright}s primary cutaneous T cell lymphomas, with Mycosis Fungoides and S{\'e}zary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) is a crucial enzyme that catalyses the biosynthesis of fatty acids, which has been reported to play an oncogenic role in various malignancies but not in CTCL so far. Herein, we show that FASN is highly expressed in CTCL cell lines and in peripheral blood mononuclear cells (PBMCs) from CTCL patients, while it is not in PBMCs from healthy individuals. The inhibition of FASN in CTCL cell lines impairs cell viability, survival, and proliferation, but, interestingly, it also increases FASN expression. However, inhibiting sterol regulatory element binding protein (SREBP), a transcription factor that promotes the expression of FASN, partially reversed the upregulation of FASN induced by FASN inhibitors. Thus, the combination of FASN and SREBP inhibitors enhanced the effects on both CTCL cell lines and PBMCs from SS patients, where a valid inhibition on cell proliferation could be verified. Importantly, compared to non-malignant cells, primary malignant cells are more sensitive to the inhibition of FASN and SREBP, making the combination of FASN and SREBP inhibitors a promising novel therapeutic strategy in CTCL.",
keywords = "cancer therapy, CTCL, FASN, SREBP",
author = "Cheng Chi and Lisa Harth and Galera, {Marina Ram{\'i}rez} and Torrealba, {Marina Passos} and Vadivel, {Chella Krishna} and Carsten Geisler and Bonefeld, {Charlotte Menn{\'e}} and Nielsen, {Pia Rude} and Michael Bzorek and Becker, {J{\"u}rgen C.} and Gjerdrum, {Lise Mette Rahbek} and Niels {\O}dum and Anders Woetmann",
note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
doi = "10.3390/cancers14184491",
language = "English",
volume = "14",
journal = "Cancers",
issn = "2072-6694",
publisher = "M D P I AG",
number = "18",

}

RIS

TY - JOUR

T1 - Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL

AU - Chi, Cheng

AU - Harth, Lisa

AU - Galera, Marina Ramírez

AU - Torrealba, Marina Passos

AU - Vadivel, Chella Krishna

AU - Geisler, Carsten

AU - Bonefeld, Charlotte Menné

AU - Nielsen, Pia Rude

AU - Bzorek, Michael

AU - Becker, Jürgen C.

AU - Gjerdrum, Lise Mette Rahbek

AU - Ødum, Niels

AU - Woetmann, Anders

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022

Y1 - 2022

N2 - Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin’s primary cutaneous T cell lymphomas, with Mycosis Fungoides and Sézary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) is a crucial enzyme that catalyses the biosynthesis of fatty acids, which has been reported to play an oncogenic role in various malignancies but not in CTCL so far. Herein, we show that FASN is highly expressed in CTCL cell lines and in peripheral blood mononuclear cells (PBMCs) from CTCL patients, while it is not in PBMCs from healthy individuals. The inhibition of FASN in CTCL cell lines impairs cell viability, survival, and proliferation, but, interestingly, it also increases FASN expression. However, inhibiting sterol regulatory element binding protein (SREBP), a transcription factor that promotes the expression of FASN, partially reversed the upregulation of FASN induced by FASN inhibitors. Thus, the combination of FASN and SREBP inhibitors enhanced the effects on both CTCL cell lines and PBMCs from SS patients, where a valid inhibition on cell proliferation could be verified. Importantly, compared to non-malignant cells, primary malignant cells are more sensitive to the inhibition of FASN and SREBP, making the combination of FASN and SREBP inhibitors a promising novel therapeutic strategy in CTCL.

AB - Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin’s primary cutaneous T cell lymphomas, with Mycosis Fungoides and Sézary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) is a crucial enzyme that catalyses the biosynthesis of fatty acids, which has been reported to play an oncogenic role in various malignancies but not in CTCL so far. Herein, we show that FASN is highly expressed in CTCL cell lines and in peripheral blood mononuclear cells (PBMCs) from CTCL patients, while it is not in PBMCs from healthy individuals. The inhibition of FASN in CTCL cell lines impairs cell viability, survival, and proliferation, but, interestingly, it also increases FASN expression. However, inhibiting sterol regulatory element binding protein (SREBP), a transcription factor that promotes the expression of FASN, partially reversed the upregulation of FASN induced by FASN inhibitors. Thus, the combination of FASN and SREBP inhibitors enhanced the effects on both CTCL cell lines and PBMCs from SS patients, where a valid inhibition on cell proliferation could be verified. Importantly, compared to non-malignant cells, primary malignant cells are more sensitive to the inhibition of FASN and SREBP, making the combination of FASN and SREBP inhibitors a promising novel therapeutic strategy in CTCL.

KW - cancer therapy

KW - CTCL

KW - FASN

KW - SREBP

U2 - 10.3390/cancers14184491

DO - 10.3390/cancers14184491

M3 - Journal article

C2 - 36139650

AN - SCOPUS:85138748473

VL - 14

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 18

M1 - 4491

ER -

ID: 323858938