Potential Tumor Suppressor Role of Polo-like Kinase 5 in Cancer

SIMPLE SUMMARY: Cancer is a complex disease and the underlying molecular mechanisms driving cancer initiation and progression is crucial for the development of effective approaches for cancer management. Exploring the molecular landscape of cancer can shed light on novel biomarkers, therapeutic targets, and strategies for personalized medicine. In this study, we determined the potential involvement of PLK5 in multiple cancers employing cancer tissue microarrays (TMAs). We found a downregulation of PLK5 in these cancers. Further, using publicly available GTEx and TCGA databases, we validated our findings and extended our investigations to additional cancer types. Overall, our data suggested a potential tumor suppressor role for PLK5. ABSTRACT: The polo-like kinase (PLK) family of serine/threonine kinases contains five members (PLK1–5). Most PLKs are involved in cell cycle regulation and DNA damage response. However, PLK5 is different as it lacks a functional kinase domain and is not involved in cell cycle control. PLK5 remains the least-studied family member, and its role in oncogenesis remains enigmatic. Here, we identified tissues with high PLK5 expression by leveraging the Protein Atlas and GTEx databases with relevant literature and selected ovarian, lung, testis, endometrium, cervix, and fallopian tube tissues as candidates for further investigation. Subsequently, we performed immunohistochemical staining for PLK5 on multiple tissue microarrays followed by Vectra scanning and quantitative inForm analysis. This revealed consistently downregulated PLK5 expression in these cancers compared to normal tissues. To validate and extend our findings, we performed pan-cancer analysis of PLK5 expression using public RNAseq databases (TCGA and GTEx). We found PLK5 is downregulated in 18 cancer types, including our selected candidates. Interestingly, we also observed PLK5 expression remains consistently low in later stages of cancer, suggesting PLK5 may have a greater role in tumor initiation than cancer progression. Overall, our study demonstrates PLK5 downregulation in multiple cancers, highlighting its role as a tumor suppressor.