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Dualistic Effects of PRKAR1A as a Potential Anticancer Target in Cancer Cells and CancerDerived Stem Cells. Int. J. Mol. Sci. 2024, 25, 2876. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25052876](10.3390/ijms25052876)  \nAcademic Editor: Akiyoshi Takami  \nReceived: 21 January 2024  \nRevised: 21 February 2024  \nAccepted: 28 February 2024  \nPublished: 1 March 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Republic of Korea; [wkdqordnjs55@gmail.com](wkdqordnjs55@gmail.com)  \n2 Department of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; [arbjlvz@snu.ac.kr](arbjlvz@snu.ac.kr)  \n3 Department of Convergence Medicine, Asan Medical Center, Seoul 05505, Republic of Korea  \n* Correspondence: [kkkon1@amc.seoul.kr](kkkon1@amc.seoul.kr) (K.K.); [kimph1010@konyang.ac.kr](kimph1010@konyang.ac.kr) (P.-H.K.); Tel.: +82-42-600-8436 (P.-H.K.); Fax: +82-42-600-8408 (P.-H.K.)  \nAbstract: The integration of innovative medical technologies and interdisciplinary collaboration could improve the treatment of cancer, a globally prevalent and often deadly disease. Despite recent advancements, current cancer therapies fail to specifically address recurrence and target cancer stem cells (CSCs), which contribute to relapse. In this study, we utilized three types of cancer cells, from which three types of CSCs were further derived, to conduct a proteomic analysis. Additionally, shared cell surface biomarkers were identified as potential targets for a comprehensive treatment strategy. The selected biomarkers were evaluated through short hairpin RNA treatment, which revealed contrasting functions in cancer cells and CSCs. Knockdown of the identified proteins revealed that they regulate the epithelial–mesenchymal transition (EMT) and stemness via the ERK signaling pathway. Resistance to anticancer agents was consequently reduced, ultimately enhancing the overall anticancer effects of the treatment. Additionally, the significance of these biomarkers in clinical patient outcomes was confirmed using bioinformatics. Our study suggests a novel cancer treatment strategy that addresses the limitations of current anticancer therapies.  \nKeywords: cancer; cancer stem cells; proteomic analysis; new biomarkers; dualistic effect  \n1. Introduction  \nCancer is a globally prevalent disease that accounts for approximately 25% of all deaths in most developed countries, making it the leading cause of death worldwide [1,2] . It can metastasize to other tissues and organs, which makes it difficult to cure [3] . Cancer-derived stem cells (CSCs) constitute a small population of cancer cells and are important in cancer treatment. This cell population accounts for 1–2% of cancer tissue and plays a pivotal role in cancer recurrence post treatment.  \nHowever, unlike normal stem cells, they can initiate tumor formation (tumorigenicity), propagate tumors throughout the body, and undergo unlimited self-renewal [4,5] . Typically existing in a dormant state, CSCs demonstrate resistance to anticancer drugs. This poses a formidable obstacle to their eradication during cancer therapy and considerably contributes to cancer relapse and metastasis [6] . Consequently, comprehensive cancer treatment requires the targeted removal of both cancer cells and CSCs.  \nIn recent years, research into targeted c","cbCaiqPo8VFYwarY","https://ap.wps.com/l/cbCaiqPo8VFYwarY","pdf",10217198,29,"English","# Introduction\n## Background on cancer and cancer-derived stem cells (CSCs)\n## Limitations of current targeted therapies\n## Rationale for biomarker discovery and proteomic analysis","[{\"question\":\"Why are cancer-derived stem cells (CSCs) important for cancer treatment outcomes?\",\"answer\":\"CSCs are a small subpopulation that drives tumor recurrence after therapy. They initiate tumors, support widespread tumor propagation, and resist anticancer drugs, contributing to relapse and metastasis.\"},{\"question\":\"How did the study identify potential targets for treatment?\",\"answer\":\"The study used proteomic analysis on multiple cancer cell types and corresponding CSCs. It identified shared cell-surface biomarkers and evaluated them through short hairpin RNA treatment.\"},{\"question\":\"What did biomarker knockdown reveal about signaling and cancer behaviors?\",\"answer\":\"Knockdown of the identified proteins regulated epithelial–mesenchymal transition (EMT) and stemness via the ERK signaling pathway. It also reduced resistance to anticancer agents, enhancing overall anticancer effects.\"}]","Dualistic Effects of PRKAR1A as a Potential Anticancer Target in Cancer Cells and Cancer-Derived Stem Cells | PDF",1789987850,73]