Breast cancer surpassed lung cancer to become the world's most common cancer in 2020. Compared with non-triple-negative breast cancer, triple-negative breast cancer has a very poor prognosis due to the lack of effective clinical treatment methods. In 2017, using the Sleeping Beauty transposable system, Chen Liming's group published a research paper in "PNAS" to report a batch of breast cancer driver genes, including the PRKD3 gene (full text link: https://www.pnas.org/content/pnas /114/11/E2215.full.pdf). Further studies by his group suggests that the PRKD3 signaling pathway plays a key role in triple-negative breast cancer and may be used as a drug target to against triple-negative breast cancer (IJBS, 2017; CM, 2019; CBP, 2019; JCMM, 2020; JC, 2021). However, the core molecular mechanism of PRKD3 in regulating triple-negative breast cancer and related intervention strategies have yet to be studied and developed, respectively. Recently, his group made important progresses and published a research paper entitled "Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple-Negative Breast Cancer Tumor Growth" in a high-impact academic journal-Advanced Science (Impact Factor: 15.840).
In this paper, the research team discovered CLU as the key molecule for PRKD3 in regulating the growth of triple-negative breast cancer through mass spectrometry screening. Combined with the cross-study using "oncology", "biology" and "pharmacy", the mechanism was explored and potential new comprehensive diagnosis and treatment strategy for triple-negative breast cancer was developed. In terms of basic theory, this study further confirmed that PRKD3 is highly expressed in triple-negative breast cancer and plays a key role in promoting the growth of triple-negative breast cancer, where PRKD3 promotes the growth of triple-negative breast cancer by inhibiting CLU lysosome degradation and stabilizing CLU. In terms of transformational applications, the study confirmed that nearly 90% of triple-negative breast cancers are PRKD3+ and/or CLU+. Drug targeting PRKD3 or CLU can achieve up to 95% growth suppression of triple-negative breast tumors in various preclinical animal models, including PDX models. Secreted CLU can be used as a blood-based molecular marker for the diagnosis and classification of triple-negative breast cancer and the efficacy evaluation after targeted drug therapy. To sum up, this research reveals the key role and mechanism of PRKD3-CLU signal axis in promoting the growth of triple-negative breast cancer to provide a comprehensive understanding of potential triple-negative breast cancer. What’s more, the developed new strategy for diagnosis and treatment for triple-negative breast cancer has important clinical significance to provide theoretical and technical support for the subsequent breakthrough of the clinical treatment of triple-negative breast cancer.
Chen Liming's group has been engaged in mechanism behind tumor pathogenesis and related intervention strategies for years using multidisciplinary tools. In recent years, his group has mainly focused on breast cancer. His previous multidisciplinary research data have been published in journals such as BCR, G & D, JBC, Bioinformatics, NSMB and PNAS.
This research work was funded by scientific research projects, including the National Natural Science Foundation of China and Natural Science Fund for Distinguished
Young Scholars of Jiangsu Province. Dr. Liu Yan is the first author, Professor Chen Liming is the corresponding author, and the corresponding author affiliation is Nanjing Normal University. Link to the paper: https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202003205. Nanjing Normal University has filed patent applications related to this work, listing L.C., Y.L., and J.Z. as inventors, where Professor Chen Liming is the first inventor (Patent No.: 202011228037.1).