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Table of contents Table of abbreviations .................................................................................................................................. 8 1) Abstract .....................................................................

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Table of contents

Table of abbreviations ... 8 1) Abstract ... 11 2) Résumé ... 12 3) Introduction ... 13

3A) Skin biology ... 13

3AA) Embryogenesis ... 14

3AAa) Epidermal specification ... 14

3AAb) Hair follicle embryogenesis ... 19

3AB) Homeostasis ... 20

3Aba) Stem cells ... 20

3AD) Skin cancers ... 30

3ADa) Basal cell carcinoma ... 31

3ADa2) Cell of origin ... 33

3B) Sox9 ... 38

3BA) Molecular characteristics ... 38

3Bb) SOX9 in embryogenesis ... 40

3Bc) Sox9 in epidermis ... 41

3Bd) SOX9 in cancer ... 44

3C) Resistance to therapy ... 47

3CBb) Mechanisms of resistance to therapy ... 48

3CBba) Drug efflux ... 48

3CBbb) Drug activation or inactivation ... 49

3CBbc) Alteration of drug targets ... 49

3CBbf) Redundancy ... 52

3CBbh) Cancer stem cells ... 54

3D) Resistance to therapy in BCC ... 56

4B) Lgr5 in adult tissues ... 59

4C) Lgr5 in cancer and cancer stem cells ... 60

5A) Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion 60 First paper: Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion... 65

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Second paper: A slow cycling Lgr5 tumor cell population mediates resistance to Smoothened inhibitor

in Basal Cell Carcinoma ... 69

6) Discussion ... 70

7. Perspectives. ... 81

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