title: SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma.
abstract: Although the principles that balance stem cell self-renewal and differentiation in normal tissue homeostasis are beginning to emerge, it is still unclear whether cancer cells with tumour initiating potential are similarly governed, or whether they have acquired distinct mechanisms to sustain self-renewal and long-term tumour growth. Here we show that the transcription factor Sox2, which is not expressed in normal skin epithelium and is dispensable for epidermal homeostasis, marks tumour initiating cells (TICs) in cutaneous squamous cell carcinomas (SCCs). We demonstrate that Sox2 is required for SCC growth in mouse and human, where it enhances Nrp1/Vegf signalling to promote the expansion of TICs along the tumour-stroma interface. Our findings suggest that distinct transcriptional programmes govern self-renewal and long-term growth of TICs and normal skin epithelial stem and progenitor cells. These programmes present promising diagnostic markers and targets for cancer-specific therapies.
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: Jasmin M
authors: JM
authors: Siegle
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: Alice
authors: A
authors: Basin
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: Ana
authors: A
authors: Sastre-Perona
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: Yoshiya
authors: Y
authors: Yonekubo
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: Jessie
authors: J
authors: Brown
authors: Department of Developmental and Regenerative Biology, Department of Dermatology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors: Rachel
authors: R
authors: Sennett
authors: Department of Developmental and Regenerative Biology, Department of Dermatology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors: Michael
authors: M
authors: Rendl
authors: Department of Pathology, Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, New York 10016, USA.
authors: Aristotelis
authors: A
authors: Tsirigos
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: John A
authors: JA
authors: Carucci
authors: The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, New York University Langone Medical Center, New York 10016, New York, USA.
authors: Markus
authors: M
authors: Schober
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D059016:Tumor Microenvironment / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1