2020 PPP magazine

2020 Paint the Paper Pink Lincoln Daily News October 2020 Page 47 targeting kinases in the PI3K-AKT pathway, which has seen limited efficacy due to both on- and off-target side effects, we may be able to inhibit the PRL2 phosphatase and restore levels of PTEN to suppress tumor formation. That’s exciting and could impact many forms of cancer.” Kinases attach phosphate groups to proteins while phosphatases remove them, and both have the potential to change proteins in ways that turn cells cancerous. Zhang’s team showed that PRL2 removes a phosphate from tyrosine 336 in PTEN. When that happens, PTEN is ubiquitinated, or essentially marked for degradation, lowering its levels and ability to fight cancer progression. The scientists discovered that high PRL2 expression is correlated with low PTEN level and reduced overall patient survival in several human malignancies. When PRL2 was deleted from a cancer-prone, PTEN-deficient mouse model, PTEN levels returned to normal and cancer progression ceased. “This sheds light on how PRL2 causes cancer and validates it as a target for PTEN- restoration therapy,” said Zhang, who is a member of the Purdue Center for Cancer Research. “It also shows the potential for looking not only to kinases as a way to inhibit tumorigenesis, but also to phosphatases.” Zhang’s lab earlier identified a promising method for PRL2 inhibition. PRL2 functions as a trimer, and the molecule Cmdp-43 has been shown to disrupt the ability of PRL2 to come together. Zhang is continuing development of the drug. The National Institutes of Health and the Robert C. and Charlotte Anderson Chair Endowment provided funding for Zhang’s research. [Writer: Brian Wallheimer Source: Zhong-Yin Zhang] The ACS is currently funding the following research at Purdue University: Targeting Matrix-Mediated Drug Resistance in Metastatic Breast Cancer - $792,000