title: Sox2 cooperates with Lkb1 loss in a mouse model of squamous cell lung cancer.
abstract: Squamous cell carcinoma (SCC) of the lung is the second most common subtype of lung cancer. With limited treatment options, the 5-year survival rate of SCC is only 15%. Although genomic alterations in SCC have been characterized, identifying the alterations that drive SCC is critical for improving treatment strategies. Mouse models of SCC are currently limited. Using lentiviral delivery of Sox2 specifically to the mouse lung, we tested the ability of Sox2 to promote tumorigenesis in multiple tumor suppressor backgrounds. Expression of Sox2, frequently amplified in human SCC, specifically cooperates with loss of Lkb1 to promote squamous lung tumors. Mouse tumors exhibit characteristic histopathology and biomarker expression similar to human SCC. They also mimic human SCCs by activation of therapeutically relevant pathways including STAT and mTOR. This model may be utilized to test the contribution of additional driver alterations in SCC, as well as for preclinical drug discovery.
authors: Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
authors: Anandaroop
authors: A
authors: Mukhopadhyay
authors: Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
authors: Kristofer C
authors: KC
authors: Berrett
authors: Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
authors: Ushma
authors: U
authors: Kc
authors: Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
authors: Phillip M
authors: PM
authors: Clair
authors: Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
authors: Stelian M
authors: SM
authors: Pop
authors: Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA.
authors: Shamus R
authors: SR
authors: Carr
authors: ARUP Laboratories, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84112, USA.
authors: Benjamin L
authors: BL
authors: Witt
authors: Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA. Electronic address: trudy.oliver@hci.utah.edu.
authors: Trudy G
authors: TG
authors: Oliver
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D055748:SOXB1 Transcription Factors; D050791:STAT Transcription Factors; C527783:Sox2 protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases