1.Cell Rep: Uncovering the new molecular mechanism of tumor suppressor p53-induced cancer cell death
doi: 10.1016 / j.celrep.2020.03.011
There has been an ongoing battle between cancer cells and p53. P53 is known as the “guardian of the genome.” The researchers have deeply analyzed two cancer treatment scenarios. In the first scenario, cancer cells will stop proliferating, while in another scenario, cancer cell mortality will increase, and both outcomes will be regulated by p53 protein. Based on the research findings in this article, the researchers discovered a special protein factor called DHX30, which can help determine whether p53 will induce cancer cell death. In addition, the researchers focused on a new type of molecular mechanism similar to the switch related research.
2.Nature: reveal p53 deficiency promotes head and neck cancer recruitment of neurons to promote cancer growth and progression mechanism
doi: 10.1038 / s41586-020-1996-3
Researchers from the university of Texas MD Anderson cancer center in the United States report a lack of an important tumor suppressor gene that allows head and neck cancers to send signals to nearby nerves, alter their function and recruit them to tumors, where they promote cancer growth and progression. By cracking the mechanism that initiates neuronal invasion of tumors, a known marker of poor patient prognosis, they discovered ways that they might prevent this process, including the use of drugs commonly used to treat blood pressure and arrhythmias.
The researchers said that a large number of studies have shown that patients with many nerves in the tumor are getting worse and worse, with a higher recurrence rate and shorter survival time. Nerve endings found in surgically resected tumors are not easily characterized or traced to their origin, so this is a neglected area, a neglected cancer feature. When surgeons remove head and neck cancer and find a high degree of nerve invasion, sometimes postoperative radiotherapy is effective. But we really don’t yet know whether the tumor is growing in the nerve or the nerve growing in the tumor, and what signals are driving these interactions.
3. iScience: revealing the mechanism of p53-related cancer chemotherapy resistance
doi: 10.1016 / j.isci.2020.100820
Globally, more than half of cancer cases are related to mutations in the p53 gene, and the protein they produce protects DNA from cancer-induced changes. When the protein is deformed, it will not only lose its protective capacity, but also produce new functions. It will play the role of a “traitor”, and promote the spread of tumors by forming protein clusters that may be resistant to chemotherapy. Researchers are currently unclear about the mechanism by which this occurs and how it develops drug resistance. Scientists have identified a large number of “traitor” proteins in chemotherapy-resistant cells derived from glioblastoma. At the same time, researchers have revealed how these proteins are deformed to resist therapy, which can form more than in healthy individuals. Larger sized clumps, some of which also have amyloid properties (when mutations induce clumps). In this study, the researchers observed these changes in the nucleus of living cells for the first time.
4. Science sub-Journal: Using synthetic mRNA nanoparticles to restore p53 can make cancers lacking p53 sensitive to mTOR inhibitors
doi: 10.1126 / scitranslmed.aaw1565
The researchers found that restoring p53 not only delayed the growth of liver cancer cells and lung cancer cells lacking p53, but also made the tumor more sensitive to cancer drugs called mTOR inhibitors. In preclinical experiments, these researchers used synthetic mRNA nanoparticles to restore p53, making lung cancer cells and liver cancer cells sensitive to existing cancer drugs. The evidence provided in this new study suggests that the lipid-polymer hybrid mRNA nanoparticle platform developed by the researchers to restore p53 may make cancer cells sensitive to mTOR inhibitors. This represents a potentially powerful combination of cancer treatments.
5. Nature: Reveals that α-ketoglutarate is a p53-mediated tumor suppressor effector
doi: 10.1038 / s41586-019-1577-5
The researchers found that p53 reshapes cancer cell metabolism, thereby promoting changes in chromatin and gene expression in favor of maintaining premalignant cell fate. Restoration of p53 function in cancer cells derived from a PDAC mouse model with KRAS mutations results in the accumulation of α-ketoglutarate (αKG), where αKG can also serve as a specific substrate for some chromatin modifying enzymes.
6. Cell Rep: Reveal new patterns and functions of p53 mutations in cancer
doi: 10.1016 / j.celrep.2019.07.001
The researchers studied the cancer genome map of 10,225 patients, containing samples of 32 different cancers, and compared them with data from another database containing 80,000 mutations. Through the analysis of this large data sample, they have a deeper understanding of how TP53 gene mutations affect cancer. The team found that TP53 mutations were more frequent in patients with lower survival rates among all cancer types studied. But they also found a way to predict the prognosis more accurately. The researchers found four up-regulated genes in mutated TP53 tumors, and their expression is related to the prognosis of patients.
7. Nature: p53 deletion leads to breast cancer metastasis by triggering systemic inflammation
doi: 10.1038 / s41586-019-1450-6
The researchers used 16 different mouse models of breast cancer genetic engineering to reveal the role of cancer cell-specific p53 as a key regulator of metastatic neutrophils. The researchers demonstrated that there is a mechanistic link between the loss of p53 in cancer cells, the secretion of WNT ligands, and systemic neutropenia, which increases the rate of metastasis. These findings clarify the importance of breast cancer gene composition in determining metastatic systemic inflammation and lay the foundation for personalized immune intervention strategies for cancer patients.
8. Nature: Tsinghua University’s Jiang Peng research group reveals the mechanism by which cancer cells regulate ammonia metabolism through p53
doi: 10.1038 / s41586-019-0996-7
The researchers reported that p53, the most frequently mutated tumor suppressor gene in human tumors, regulates ammonia metabolism by inhibiting the urea cycle. By transcriptionally down-regulating the genes CPS1, OTC and ARG1, p53 inhibits ureagenesis and ammonia clearance in vitro and in vivo, thereby inhibiting tumor growth. In turn, the down-regulation of these genes activates p53 through a mechanism mediated by MDM2.
9. Cancer Cell: A major breakthrough! The tumor suppressor gene p53 actually promotes tumor growth!
doi: 10.1016 / j.ccell.2018.12.012
The researchers found that WTp53 can stimulate tumor growth by enhancing cancer metabolism, the key of which is a protein called PUMA (p53 positive apoptosis regulator), which can play a role in mitochondria; at appropriate levels, PUMA can interfere with the normal function of mitochondria and promote the conversion of oxidative phosphorylation process to glycolysis process. Researcher Professor Xu said that one widely accepted view today is that p53 inhibits cancer, but in this study, we found that in some cancers, p53 has the opposite effect, which is to promote cancer.
10. Nat Cell Biol: Scientists identify new role of tumor suppressor gene p53
doi: 10.1038 / s41556-019-0297-2
Scientists have discovered through research that the p53 protein may play an unexpected role, and the relevant research results may provide new ideas for the development of new drugs to treat cancer. p53 is like Janus, the two-faced god of ancient Rome. It is the most frequently mutated gene in many cancers. When it is mutated, it will transform its role from a tumor suppressor to an oncogene, thus driving most cancers . The p53 protein can act as a “guard” for the genome. It will start the repair process of DNA damage caused by ultraviolet radiation, chemicals, etc. However, when the protein is mutated, it will be out of control and become less mutated. Similar proteins are more stable and easily accumulate in the nucleus, eventually causing cancer. In this study, the researchers discovered a novel mechanism driving the stability of the mutant p53 protein, namely the enzyme named PIPK1-α and its lipid messenger PIP2, which seem to behave like the main regulator of p53.