title: Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk.
abstract: A fundamental goal in cancer biology is to identify the cells and signalling pathways that are keys to induce tumour regression. Here we use a spontaneously self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify physiological mechanisms that drive tumour regression. By using a mouse model system that recapitulates the behaviour of human KAs, we show that self-regressing tumours shift their balance to a differentiation programme during regression. Furthermore, we demonstrate that developmental programs utilized for skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour growth and that the retinoic acid (RA) signalling pathway promotes tumour regression by inhibiting Wnt signalling. Finally, we find that RA signalling can induce regression of malignant tumours that do not normally spontaneously regress, such as squamous cell carcinomas. These findings provide new insights into the physiological mechanisms of tumour regression and suggest therapeutic strategies to induce tumour regression.
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zito
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Ichiko
authors.initials: I
authors.lastname: Saotome
authors.affiliation: Department of Pathology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Enrico G
authors.initials: EG
authors.lastname: Ferro
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Thomas Y
authors.initials: TY
authors.lastname: Sun
authors.affiliation: Department of Pathology, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Don X
authors.initials: DX
authors.lastname: Nguyen
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bilguvar
authors.affiliation: Department of Dermatology, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Ko
authors.affiliation: 1] Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut 06510, USA [2] Department of Dermatology, Yale School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Greco
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D004195:Disease Models, Animal; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D007636:Keratoacanthoma / Q000378:metabolism*; D051379:Mice; D012075:Remission, Spontaneous; D012878:Skin Neoplasms / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D014212:Tretinoin