A domestic research team has found the link between cancer tissue’s size growth and degree of metastasis to other tissues.
The research paper, titled “Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner,” was published in Nature Communications.
It is generally believed that the rate of cancer spreading to surrounding tissues and lymph nodes is high when cancer tissue develops and its size grows. However, the cause and effect relationship between cancer tissue metastasis and proliferation has not been clarified, as seen by cases where cancer metastasized even when cancer tissue size was small.
The team, led by Professors Yook Jong-in and Kim Hyun-sil from Yonsei University College of Dentistry, Oral Pathology, found the regulating process of the signaling system that controls cancer metastasis and proliferation through a cell and in vivo animal experiments as well as clinical data analysis experiments.
The researchers set up and repeatedly tested a hypothesis where they believed clarifying the reciprocal regulation relationship between Hippo signaling that regulates cancer proliferation and Wnt signaling involved in cancer metastasis would lead to the discovery of the correlation between the size of the cancer tissue growth and the degree of metastasis.
They found Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated Yes-associated protein (YAP).
Namely, the DVL combines with phosphorylated nuclear YAP and transports it to outside the nucleus, inhibiting the activation process of nuclear YAP. In case DVL did not inhibit nuclear YAP, both the Wnt signaling and nuclear YAP became activated simultaneously, leading to evident growth in cancer tissue.
The research team also found that deficit of the P53 or LKB1 gene within the cancer tissue relieves DVL-linked reciprocal inhibition between the Wnt and nuclear YAP activity, letting both Wnt and nuclear YAP activity be activated simultaneously.
"The research clarified the signaling regulating mechanism that organically controls cancer cell metastasis and proliferation and raises expectations of providing a related index that allows for cancer prognosis and prediction," Professor Yook said.