Breakthroughs in Ovarian Cancer


Deanna Csomo McCool | October 1, 2017

Two papers involving ovarian cancer research at the University of Notre Dame’s Harper Cancer Research Institute (HCRI), one featuring new research and the other a review article, were published as cover stories in their respective journals.
M. Sharon Stack, the Anne F. Dunne and Elizabeth Riley Director of HCRI, along with postdoctoral researchers Jing Yang and Yuliya Klymenko, among others, have been studying why ovarian cancer cells uniquely spread throughout the peritoneal cavity. Within that abdominal space, shed ovarian cancer cells bind together, forming lethal structures called aggregates. Those aggregates float in the cavity until eventually sticking and penetrating more tissues. This mode of metastasis, along with vague symptoms that cause diagnostic delays, makes ovarian cancer one of the most deadly cancers.
In their article published in The Journal of Biological Chemistry (JBC), Yang, Stack and colleagues studied a membrane proteinase, called MT1-MMP, which is an enzyme that begins the breakdown of connective tissue proteins. MT1-MMP is generally not detected in normal ovarian tissue or even in benign ovarian tumors.
MT1-MMP includes a short cytoplasmic tail, or chain of 20 amino acids, that regulates activity on the cell’s surface. The tail contains three potential places where proteins are regulated, called phosphorylation sites. Yang’s and Stack’s research demonstrated that phosphorylation may play a role in regulating the transition of ovarian cancer cells from the “floating” phase to the “sticking” phase in the peritoneal cavity.
“MT1 is a molecular clipper on the surface of cells, clipping the proteins out of the way just like we would clip away roots of a tree to allow more room for other plants,” Stack said. “For ovarian cancer cells, this makes them stick better and gives them room to thrive.” And becoming stickier means more metastatic success — effectively spreading the cancer to new areas of the body.
The discovery is important because understanding how the different phosphorylation sites function could lead to drug discoveries that target and inhibit the process, Stack said.

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 by Daily Domer Staff

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