Spontaneous Tumour Regression in Keratoacanthomas is Driven by Wnt/retinoic Acid Signalling Cross-talk

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Mar 27

PMID 24667544

Citations 32

Authors

Giovanni Zito

Ichiko Saotome

Zongzhi Liu

Enrico G Ferro

Thomas Y Sun

Don X Nguyen

Kaya Bilguvar

Christine J Ko

Valentina Greco

Affiliations

Soon will be listed here.

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.

Citing Articles

Keratoacanthoma versus Squamous-Cell Carcinoma: Histopathological Features and Molecular Markers.

Bahmad H, Stoyanov K, Mendez T, Trinh S, Terp K, Qian L Dermatopathology (Basel). 2024; 11(4):272-285.

PMID: 39449378 PMC: 11503433. DOI: 10.3390/dermatopathology11040029.

Retinoic acid drives hair follicle stem cell activation via Wnt/β-catenin signalling in androgenetic alopecia.

Wen L, Fan Z, Huang W, Miao Y, Zhang J, Liu B J Eur Acad Dermatol Venereol. 2024; 39(1):189-201.

PMID: 38629345 PMC: 11664453. DOI: 10.1111/jdv.20000.

Multiple Keratoacanthoma-like Syndromes: Case Report and Literature Review.

Karampinis E, Kostopoulou C, Toli O, Marinos L, Papadimitriou G, Roussaki Schulze A Medicina (Kaunas). 2024; 60(3).

PMID: 38541097 PMC: 10972420. DOI: 10.3390/medicina60030371.

Distinguishing Keratoacanthoma from Well-Differentiated Cutaneous Squamous Cell Carcinoma Using Single-Cell Spatial Pathology.

Veenstra J, Ozog D, Loveless I, Adrianto I, Dimitrion P, Subedi K J Invest Dermatol. 2023; 143(12):2397-2407.e8.

PMID: 37419445 PMC: 10840781. DOI: 10.1016/j.jid.2023.06.192.

An Updated Review of the Therapeutic Management of Keratoacanthomas.

Ambur A, Clark A, Nathoo R J Clin Aesthet Dermatol. 2023; 15(12 Suppl 1):S16-S22.

PMID: 36588786 PMC: 9769584.

References

Froeling F, Feig C, Chelala C, Dobson R, Mein C, Tuveson D . Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt-β-catenin signaling to slow tumor progression. Gastroenterology. 2011; 141(4):1486-97, 1497.e1-14. DOI: 10.1053/j.gastro.2011.06.047. View

Gat U, Dasgupta R, Degenstein L, Fuchs E . De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell. 1998; 95(5):605-14. DOI: 10.1016/s0092-8674(00)81631-1. View

Foitzik K, Spexard T, Nakamura M, Halsner U, Paus R . Towards dissecting the pathogenesis of retinoid-induced hair loss: all-trans retinoic acid induces premature hair follicle regression (catagen) by upregulation of transforming growth factor-beta2 in the dermal papilla. J Invest Dermatol. 2005; 124(6):1119-26. DOI: 10.1111/j.0022-202X.2005.23686.x. View

Muzumdar M, Tasic B, Miyamichi K, Li L, Luo L . A global double-fluorescent Cre reporter mouse. Genesis. 2007; 45(9):593-605. DOI: 10.1002/dvg.20335. View

Sinnberg T, Menzel M, Ewerth D, Sauer B, Schwarz M, Schaller M . β-Catenin signaling increases during melanoma progression and promotes tumor cell survival and chemoresistance. PLoS One. 2011; 6(8):e23429. PMC: 3157382. DOI: 10.1371/journal.pone.0023429. View

Green J, La J, Yum K, Desai P, Rodewald L, Zhang X . Paracrine Wnt signaling both promotes and inhibits human breast tumor growth. Proc Natl Acad Sci U S A. 2013; 110(17):6991-6. PMC: 3637696. DOI: 10.1073/pnas.1303671110. View

Nakagawara A . Molecular basis of spontaneous regression of neuroblastoma: role of neurotrophic signals and genetic abnormalities. Hum Cell. 1999; 11(3):115-24. View

Hardy M . The secret life of the hair follicle. Trends Genet. 1992; 8(2):55-61. DOI: 10.1016/0168-9525(92)90350-d. View

Guasch G, Schober M, Pasolli H, Conn E, Polak L, Fuchs E . Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell. 2007; 12(4):313-27. PMC: 2424201. DOI: 10.1016/j.ccr.2007.08.020. View

10.

Blessing K, Al Nafussi A, Gordon P . The regressing keratoacanthoma. Histopathology. 1994; 24(4):381-4. DOI: 10.1111/j.1365-2559.1994.tb00541.x. View

11.

Blagosklonny M . Target for cancer therapy: proliferating cells or stem cells. Leukemia. 2005; 20(3):385-91. DOI: 10.1038/sj.leu.2404075. View

12.

Hamid Y, Poller D . Spontaneous regression of renal cell carcinoma: a pitfall in diagnosis of renal lesions. J Clin Pathol. 1998; 51(4):334-6. PMC: 500683. DOI: 10.1136/jcp.51.4.334. View

13.

Aydin F, Senturk N, Sabanciler E, Canturk M, Turanli A . A case of Ferguson-Smith type multiple keratoacanthomas associated with keratoacanthoma centrifugum marginatum: response to oral acitretin. Clin Exp Dermatol. 2007; 32(6):683-6. DOI: 10.1111/j.1365-2230.2007.02498.x. View

14.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

15.

Hebbard L, Cecena G, Golas J, Sawada J, Ellies L, Charbono A . Control of mammary tumor differentiation by SKI-606 (bosutinib). Oncogene. 2010; 30(3):301-12. PMC: 3000443. DOI: 10.1038/onc.2010.412. View

16.

Lohse M, Bolger A, Nagel A, Fernie A, Lunn J, Stitt M . RobiNA: a user-friendly, integrated software solution for RNA-Seq-based transcriptomics. Nucleic Acids Res. 2012; 40(Web Server issue):W622-7. PMC: 3394330. DOI: 10.1093/nar/gks540. View

17.

Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P . Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature. 2008; 452(7187):650-3. DOI: 10.1038/nature06835. View

18.

Jiang Y, Prunier C, Howe P . The inhibitory effects of Disabled-2 (Dab2) on Wnt signaling are mediated through Axin. Oncogene. 2007; 27(13):1865-75. PMC: 2810718. DOI: 10.1038/sj.onc.1210829. View

19.

Gupta P, Onder T, Jiang G, Tao K, Kuperwasser C, Weinberg R . Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009; 138(4):645-659. PMC: 4892125. DOI: 10.1016/j.cell.2009.06.034. View

20.

Corominas M, Sloan S, Leon J, Kamino H, Newcomb E, Pellicer A . ras activation in human tumors and in animal model systems. Environ Health Perspect. 1991; 93:19-25. PMC: 1568045. DOI: 10.1289/ehp.919319. View