RESEARCH: CANCER
FOLDING PROJECT #15217 PROFILE

This project looks at how PTCH1 moves cholesterol in cells. PTCH1 keeps cancer-causing signals in check, but if it doesn't move cholesterol right, it can lead to cancers like medulloblastoma and basal cell carcinoma. Understanding this process could help us develop new cancer treatments.

This project aims to elucidate the cholesterol transport mechanism in PTCH1, a transmembrane protein responsible for inhibiting SMO in the absence of SHH in the hedgehog signaling pathway by reducing access to ciliary membrane cholesterol.

Dysregulation of this pathway (such as the inability of PTCH1 to transport cholesterol and thereby inhibit SMO) has been linked to various cancers, including medulloblastoma and basal cell carcinoma.

Thus, understanding the mechanisms behind PTCH1 cholesterol transport will allow for therapeutic treatments to target these cancers.

PTCH1

Patched 1, a transmembrane protein

PTCH1 is a crucial protein that acts as a brake in the Hedgehog signaling pathway. It normally binds to cholesterol and inhibits SMO (Smoothened), another key protein in the pathway. When Hedgehog signals are absent, PTCH1 keeps SMO inactive. However, if PTCH1 malfunctions or can't transport cholesterol properly, SMO becomes overactive, leading to uncontrolled cell growth and contributing to various cancers.

SMO

Smoothened

SMO is a protein that acts as a switch in the Hedgehog signaling pathway. When activated by Hedgehog signals, SMO turns on a cascade of events leading to cell growth and development. However, when inactive, SMO keeps the pathway off. The activity of SMO is tightly regulated by PTCH1.

SHH

Sonic Hedgehog

SHH is a signaling molecule that plays a vital role in embryonic development and tissue repair. It activates the Hedgehog pathway by binding to PTCH1, which then releases its inhibition on SMO.

Hedgehog Signaling Pathway

A signaling pathway crucial for development and tissue maintenance

The Hedgehog signaling pathway is a complex series of events triggered by the SHH molecule. It controls various cellular processes like cell growth, differentiation, and survival. Dysregulation of this pathway can lead to developmental abnormalities and diseases such as cancer.

Medulloblastoma

A type of brain tumor

Medulloblastoma is an aggressive type of childhood brain cancer that originates in the cerebellum. Its uncontrolled growth is often linked to dysregulation of the Hedgehog signaling pathway.

Basal Cell Carcinoma

A type of skin cancer

Basal cell carcinoma is the most common type of skin cancer. It often arises from sun damage and can be linked to mutations in genes involved in the Hedgehog signaling pathway.