RESEARCH: CANCER
FOLDING PROJECT #15210 PROFILE

This project looks at how PTCH1 moves cholesterol to block cancer-causing signals. When PTCH1 doesn't work right, cancers like medulloblastoma and basal cell carcinoma can grow. Understanding how PTCH1 works could lead to 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 involved in hedgehog signaling.

PTCH1 is a crucial protein that acts as a receptor for the hedgehog signaling pathway. It normally inhibits SMO (Smoothened) by restricting cholesterol access to the cilia membrane when there's no hedgehog signal. However, when hedgehog signals are present, PTCH1 releases its inhibition on SMO, leading to cancer development if dysregulated.

SMO

Smoothened

SMO is a protein that acts as a key component of the hedgehog signaling pathway. When PTCH1 is inhibited by hedgehog signals, SMO becomes activated, leading to downstream effects that promote cell growth and proliferation. Dysregulation of SMO contributes to various cancers.

SHH

Sonic Hedgehog

SHH is a signaling protein crucial for embryonic development and tissue repair. It activates the hedgehog pathway by binding to PTCH1, leading to SMO activation and downstream effects on cell growth and differentiation. Aberrant SHH signaling is implicated in various cancers.

hedgehog signaling pathway

A cellular signaling cascade that regulates development and cell proliferation.

The hedgehog pathway is a complex network of proteins that control various cellular processes, including embryonic development, tissue regeneration, and cell growth. It involves key players like PTCH1, SMO, and SHH. Disruptions in this pathway can contribute to cancers.

medulloblastoma

An aggressive brain tumor that arises from the cerebellum.

Medulloblastoma is a childhood cancer originating in the cerebellum, a part of the brain responsible for coordination and balance. It's characterized by rapid growth and often spreads to other parts of the body. Treatment typically involves surgery, chemotherapy, and radiation therapy.

basal cell carcinoma

The most common type of skin cancer.

Basal cell carcinoma is a slow-growing skin cancer that originates in the basal cells, which produce new skin cells. It's usually curable with treatments like surgery, radiation therapy, or topical medications. While not usually life-threatening, it can spread to nearby tissues if left untreated.