Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma
Authors: Chidera V Oku
Maciej S Lesniak
Ahmet D Arslan
Ricardo E Perez
Eleanor N Fish
Gavin T Blyth
Leonidas C Platanias
Wenan Qiang
Frank Eckerdt
Guang-Yu Yang
William M Mati
Diana Saleiro
Elspeth M Beauchamp
Daniela Verzella
Leyu Sun
Ewa M Kosciuczuk
Mariafausta Fischietti
Catalina Lee-Chang
Journal: Oncogene (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SLFN5; pancreatic ductal adenocarcinoma; proliferation; tumorigenesis; outcomes
Affiliations: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA., Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA., Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy., Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Toronto General Hospital Research Institute, University Health Network and Department of Immunology, University of Toronto, Toronto, ON, Canada., Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Evanston, IL, USA., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA. ., Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. ., Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA. .

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. 

Retracted: No

PubPeer comments:
 The GAPDH bands in Figure 3d appear quite similar (but not identical) after horizontal flip. Could the authors please provide the original uncropped scan? *** ![file] , 
 I am Fausta Fischietti and I am the first author of this paper. The bands are clearly different. As requested, please see attached the uncropped image of the GAPDH blot, that makes clear that the panels were derived from the correct portions of the blot. For presentation purposes we separated PANC-1 and MIA-Pa-Ca-2 cells on the manuscript. ![file] , 
 #2 Thank you for providing the uncropped blot. This alleviates my concern. ,