Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma

Mariafausta Fischietti; Frank Eckerdt; Gavin T. Blyth; Ahmet D. Arslan; William M. Mati; Chidera V. Oku; Ricardo E. Perez; Catalina Lee-Chang; Ewa M. Kosciuczuk; Diana Saleiro; Elspeth M. Beauchamp; Maciej S. Lesniak; Daniela Verzella; Leyu Sun; Eleanor N. Fish; Guang Yu Yang; Wenan Qiang; Leonidas C. Platanias

doi:10.1038/s41388-021-01761-1

Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma

Mariafausta Fischietti, Frank Eckerdt, Gavin T. Blyth, Ahmet D. Arslan, William M. Mati, Chidera V. Oku, Ricardo E. Perez, Catalina Lee-Chang, Ewa M. Kosciuczuk, Diana Saleiro, Elspeth M. Beauchamp, Maciej S. Lesniak, Daniela Verzella, Leyu Sun, Eleanor N. Fish, Guang Yu Yang, Wenan Qiang, Leonidas C. Platanias^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

We provide evidence that a member of the human Schlafen (SLFN) family of proteins, SLFN5, is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Targeted deletion of SLFN5 results in decreased PDAC cell proliferation and suppresses PDAC tumorigenesis in in vivo PDAC models. Importantly, high expression levels of SLFN5 correlate with worse outcomes in PDAC patients, implicating SLFN5 in the pathophysiology of PDAC that leads to poor outcomes. Our studies establish novel regulatory effects of SLFN5 on cell cycle progression through binding/blocking of the transcriptional repressor E2F7, promoting transcription of key genes that stimulate S phase progression. Together, our studies suggest an essential role for SLFN5 in PDAC and support the potential for developing new therapeutic approaches for the treatment of pancreatic cancer through SLFN5 targeting.

Original language	English (US)
Pages (from-to)	3273-3286
Number of pages	14
Journal	Oncogene
Volume	40
Issue number	18
DOIs	https://doi.org/10.1038/s41388-021-01761-1
State	Published - May 6 2021

ASJC Scopus subject areas

Genetics
Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41388-021-01761-1

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Fischietti, M., Eckerdt, F., Blyth, G. T., Arslan, A. D., Mati, W. M., Oku, C. V., Perez, R. E., Lee-Chang, C., Kosciuczuk, E. M., Saleiro, D., Beauchamp, E. M., Lesniak, M. S., Verzella, D., Sun, L., Fish, E. N., Yang, G. Y., Qiang, W., & Platanias, L. C. (2021). Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma. Oncogene, 40(18), 3273-3286. https://doi.org/10.1038/s41388-021-01761-1

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title = "Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma",

abstract = "We provide evidence that a member of the human Schlafen (SLFN) family of proteins, SLFN5, is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Targeted deletion of SLFN5 results in decreased PDAC cell proliferation and suppresses PDAC tumorigenesis in in vivo PDAC models. Importantly, high expression levels of SLFN5 correlate with worse outcomes in PDAC patients, implicating SLFN5 in the pathophysiology of PDAC that leads to poor outcomes. Our studies establish novel regulatory effects of SLFN5 on cell cycle progression through binding/blocking of the transcriptional repressor E2F7, promoting transcription of key genes that stimulate S phase progression. Together, our studies suggest an essential role for SLFN5 in PDAC and support the potential for developing new therapeutic approaches for the treatment of pancreatic cancer through SLFN5 targeting.",

author = "Mariafausta Fischietti and Frank Eckerdt and Blyth, {Gavin T.} and Arslan, {Ahmet D.} and Mati, {William M.} and Oku, {Chidera V.} and Perez, {Ricardo E.} and Catalina Lee-Chang and Kosciuczuk, {Ewa M.} and Diana Saleiro and Beauchamp, {Elspeth M.} and Lesniak, {Maciej S.} and Daniela Verzella and Leyu Sun and Fish, {Eleanor N.} and Yang, {Guang Yu} and Wenan Qiang and Platanias, {Leonidas C.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = may,

day = "6",

doi = "10.1038/s41388-021-01761-1",

language = "English (US)",

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Fischietti, M, Eckerdt, F, Blyth, GT, Arslan, AD, Mati, WM, Oku, CV, Perez, RE, Lee-Chang, C, Kosciuczuk, EM, Saleiro, D , Beauchamp, EM , Lesniak, MS, Verzella, D, Sun, L, Fish, EN, Yang, GY , Qiang, W & Platanias, LC 2021, 'Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma', Oncogene, vol. 40, no. 18, pp. 3273-3286. https://doi.org/10.1038/s41388-021-01761-1

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T1 - Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma

AU - Fischietti, Mariafausta

AU - Eckerdt, Frank

AU - Blyth, Gavin T.

AU - Arslan, Ahmet D.

AU - Mati, William M.

AU - Oku, Chidera V.

AU - Perez, Ricardo E.

AU - Lee-Chang, Catalina

AU - Kosciuczuk, Ewa M.

AU - Saleiro, Diana

AU - Beauchamp, Elspeth M.

AU - Lesniak, Maciej S.

AU - Verzella, Daniela

AU - Sun, Leyu

AU - Fish, Eleanor N.

AU - Yang, Guang Yu

AU - Qiang, Wenan

AU - Platanias, Leonidas C.

PY - 2021/5/6

Y1 - 2021/5/6

N2 - We provide evidence that a member of the human Schlafen (SLFN) family of proteins, SLFN5, is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Targeted deletion of SLFN5 results in decreased PDAC cell proliferation and suppresses PDAC tumorigenesis in in vivo PDAC models. Importantly, high expression levels of SLFN5 correlate with worse outcomes in PDAC patients, implicating SLFN5 in the pathophysiology of PDAC that leads to poor outcomes. Our studies establish novel regulatory effects of SLFN5 on cell cycle progression through binding/blocking of the transcriptional repressor E2F7, promoting transcription of key genes that stimulate S phase progression. Together, our studies suggest an essential role for SLFN5 in PDAC and support the potential for developing new therapeutic approaches for the treatment of pancreatic cancer through SLFN5 targeting.

AB - We provide evidence that a member of the human Schlafen (SLFN) family of proteins, SLFN5, is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Targeted deletion of SLFN5 results in decreased PDAC cell proliferation and suppresses PDAC tumorigenesis in in vivo PDAC models. Importantly, high expression levels of SLFN5 correlate with worse outcomes in PDAC patients, implicating SLFN5 in the pathophysiology of PDAC that leads to poor outcomes. Our studies establish novel regulatory effects of SLFN5 on cell cycle progression through binding/blocking of the transcriptional repressor E2F7, promoting transcription of key genes that stimulate S phase progression. Together, our studies suggest an essential role for SLFN5 in PDAC and support the potential for developing new therapeutic approaches for the treatment of pancreatic cancer through SLFN5 targeting.

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JO - Oncogene

JF - Oncogene

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ER -

Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma

Abstract

ASJC Scopus subject areas

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