It is becoming apparent that key pathways used in development,like Hedgehog, can become involved in tumorogenesis if they arereactivated in adult tissues through mutation or other mechanisms.Sonic Hedgehog (Shh) can act in autocrine fashion causing the cellsthat produce it to grow. Normally autocrine signalling by Shh isrequired for maintenance of certain neuronal progenitor cells andhematopoietic stem cells. In fact, Shh inhibitors can reversemeduloblastomas and leukemias, which are the cancerous forms of thecells it normally regulates. Autocrine
In humans, the Shh pathway can be summarized in the followingway:
Hh --> | PTCH1 --> | SMOH --> GLI --> Hh targetgenes
Hh = hedgehog, PTCH1 = patched, SMOH = smoothened, GLI =transcription factor
1) Propose three types of mutations in components of thispathway that might lead to cancer
2) Based on hedgehog signalling, how would you propose to treatcancer arising from Shh signalling using chemotherapy
It is becoming apparent that key pathways used in development,like Hedgehog, can become involved in tumorogenesis if they arereactivated in adult tissues through mutation or other mechanisms.Sonic Hedgehog (Shh) can act in autocrine fashion causing the cellsthat produce it to grow. Normally autocrine signalling by Shh isrequired for maintenance of certain neuronal progenitor cells andhematopoietic stem cells. In fact, Shh inhibitors can reversemeduloblastomas and leukemias, which are the cancerous forms of thecells it normally regulates. Autocrine
In humans, the Shh pathway can be summarized in the followingway:
Hh --> | PTCH1 --> | SMOH --> GLI --> Hh targetgenes
Hh = hedgehog, PTCH1 = patched, SMOH = smoothened, GLI =transcription factor
1) Propose three types of mutations in components of thispathway that might lead to cancer
2) Based on hedgehog signalling, how would you propose to treatcancer arising from Shh signalling using chemotherapy
