Vers la compréhension des mécanismes moléculaires et physiopathologiques à l'origine de l'hyperactivité neuromusculaire dans le syndrome de Schwartz-Jampel

Toward the understanding of molecular and pathophysiological mechanisms leading to neuromuscular hyperactivity in Schwartz-Jampel syndrome

• Auteur / Autrice : Morgane Stum
• Direction : Anne Baron-Van Evercooren
• Type : Thèse de doctorat
• Discipline(s) : Neurosciences
• Date : Soutenance en 2007
• Etablissement(s) : Paris 6

Mots clés

Mots clés libres

Syndrome de Schwartz-Jampel

Mutation hypomorphe

Modèle murin knock-in

Acétylcholinestérase

Perlecan

Raideur musculaire

Jonction neuromusculaire

Hyperactivité

Résumé

We have demonstrated by RT-PCR, immunohistochemistry and ELISA that BMP-7 and its receptors are present in histologically normal human crypts, in aberrant crypt foci in sigmoiditis, in human colorectal tumors and in several colorectal cancer cell lines. We have also demonstrated that BMP-7 is a scatter and invasion factor. This invasive capacity of BMP-7 is independent of SMAD4 and src activity, but is associated to the cyclic activation of RhoGTPases (Rac1 and RhoA), to FAK activation (tyr925 phosphorylation associated with angiogenesis and invasion) and to MAPK/SAPK activation (JNK and ERK1/2). Taken together my PhD work strongly suggests that BMP-7 acts as dissemination and a proinvasive factor via an autocrine and paracrine mechanism. This cytokine has divergent roles on human colon cancer progression. A beneficial role, by opposing itself to inflammation and a pejorative role by helping cancer progression on the latest stages associated to invasive capacity and to adenoma-carcinoma transition