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Novel Molecular Mechanism to Shed Light on Cancer Drug Design

Researchers from the Hong Kong University of Science and Technology (HKUST) discover molecular mechanism that could provide key guidance in development of drugs for cancer.

Planar Cell Polarity (PCP) is a biological process critical for tissue development and organ function. Defects could lead to diseases such as neurological disorders, skeletal abnormalities or heart disease. Cancer cell pathophysiology is able to take of the PCP and promote its growth and expansion.

In light of this, a team led by Prof. GUO Yusong, Assistant Professor of Division of Life Science in the School of Science at HKUST, unravelled molecular mechanisms of a key protein in PCP called Frizzled-6. This protein is transported from within the cell to the surface where it regulates PCP. Understanding the molecular mechanism behind this transportation process meant scientists can now find a way to block transportation of Frizzled-6 and shut down the PCP process if it is hijacked by cancer cells, thereby hindering cancer progression.

The research team found that Frizzled-6 contained a special region known as a polybasic motif, which interacts with SAR1A. This is a key component of COPII which is a key machinery that produces vehicles that transports the protein to the Golgi apparatus. Blocking the interaction between SAR1A and Frizzled-6 can disrupt protein transportation, which in theory should be effective in hindering cancer metastasis.

“It has been known that PCP plays important role in regulating cancer’s growth, but the molecular mechanism that regulates the transport of PCP proteins was largely unclear,” said Professor Guo.

“Our study provides important insight in guiding the rational design of inhibitors to inhibit the cell surface delivery process, and offers a novel therapeutic strategy to downregulate PCP signalling for cancer treatment.” He added.

The findings were recently published in the Journal of Biological Chemistry. This work was done in collaboration with Professor Jiang Liwen at the School of Life Sciences of the Chinese University of Hong Kong and Professor Yan Yan at the Division of Life Science of HKUST. [APBN]