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Tumor-suppressing Protein Actually Promotes Cancer
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Tumor-suppressing Protein Actually Promotes Cancer

Tumor-suppressing Protein Actually Promotes Cancer
News

Tumor-suppressing Protein Actually Promotes Cancer

Credit: Tulane University
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Tulane University researchers have discovered that the protein PHLDB3, thought to be a potential tumor suppressor, actually allows cancer cells to thrive in pancreatic, prostate, colon, breast, lung, and other common cancers. The discovery could explain how cancer is able to overcome p53 – a key tumor-suppressing protein.


The findings, recently published in Nature Communications, could eventually lead to targeted diagnostic tests and treatments of certain types of cancer. 


“Now that we’ve identified the molecule, we could utilize it as an anti-cancer target,” said lead study author Dr. Hua Lu, the Reynolds and Ryan Families Chair in Translation Cancer at Tulane. “This target can be used to develop a drug that would hopefully, combined with chemotherapy, be more effective and less toxic.” 


Scientists have long known that protein p53 protects against cancer by triggering cells with DNA damage to self-destruct before they become malignant. P53 is kept in check by two genes, MDM2 and MDMX, which regulate its growth and demise. While overproduction of either the genes or the protein is harmful, a balanced production of both p53 and the genes allows for normal cell development.


Lu and his team discovered that PHLDB3 works with MDM2 to inhibit p53, promoting tumor growth. The protein could also cause therapeutic resistance for some late state cancers. 


To ensure that PHLDB3 is an optimal drug target, Lu says the next step is to further validate the cancer-causing role of PHLDB3 by using mouse model systems either dependently or independently of p53. He says it’s also important to understand the protein’s biological role in cellular signaling and normal animal development as well as to consolidate its role in human cancer development, progression and drug-resistance.


This article has been republished from materials provided by Tulane University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Tengfei Chao, Xiang Zhou, Bo Cao, Peng Liao, Hongbing Liu, Yun Chen, Hee-Won Park, Shelya X. Zeng, Hua Lu. Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53. Nature Communications, 2016; 7: 13755 DOI: 10.1038/ncomms13755
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