Cancer Scientists

AFCR-Supported Scientist Discovers Critical Molecular Interaction, Opens New Avenue for Cancer Drug Development

(Hong Kong, April 13, 2015) Prof. Mingjie Zhang of Hong Kong University of Science and Technology, a scientist supported by the Asian Fund for Cancer Research (AFCR), recently discovered a critical molecular interaction governing epithelial cell polarity – a crucial factor in tumor formation. The research, which was funded in part by AFCR, opens a new avenue to develop therapeutic methods against many types of cancer.

Epithelial cells are the most common type of cells in the human body, forming the linings and surfaces of the skin, lung, kidney, liver, stomach, intestine, reproductive system, and more. Despite this variety, one thing that all epithelial cells have in common is “polarity,” meaning that one side of the cell has a different size, shape, or function from the other side. Polarity is what allows epithelial surfaces to carry out highly specialized functions, like digesting food or filtering blood.

Polarity also plays a critical role in cancer. “More than 80% of tumors originate in epithelial cells, and this is always accompanied by loss of polarity,” says Prof. Zhang. “Understanding how epithelial cells lose polarity will provide valuable insight into why various cancers form – and how we might stop them.”

With this investigation, Prof. Zhang and his team have provided some of that insight. Although a critical molecular structure called the Crumbs complex (composed of three proteins called Crumbs, Pals1, and Patj) is known to operate as the master regulator of cell growth and polarity, it is currently unclear exactly how these proteins come together to assemble the complex. Prof. Zhang discovered that a highly specific interaction – between the tail of the Crumbs protein and a particular part of the Pals1 protein called the PDZ-SH3-GK tandem – is required to assemble the Crumbs complex and maintain epithelial cell polarity.

Intriguingly, Prof. Zhang also discovered that certain mutations – which disrupt the interaction of the Pals1 PDZ-SH3-GK and Crumbs – can compromise cell polarity. This suggests a new mechanism for tumor formation and metastasis. This discovery offers a new potential target for cancer treatment or prevention.

“Prof. Zhang’s investigation into the molecular basis of cancer helps us understand how tumors form, which in turn helps us learn how to stop them,” said AFCR President Sujuan Ba, Ph.D. “By shedding more light on this question, Prof. Zhang has laid important scientific groundwork, opening a new field for anti-cancer treatment, and bringing us closer to cures for patients.”

The investigation is published in the Proceedings of the National Academy of Sciences.