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Cancer remains a leading cause of mortality globally, highlighting the need for novel biomarkers to enhance prognosis and therapeutic strategies. Pleckstrin-2 (PLEK2), a member of the pleckstrin family, has been implicated in processes critical to tumor progression, but its role across cancers remains underexplored. This study systematically examined the expression patterns, prognostic relevance, and functional impact of PLEK2 across multiple cancer types. Using data from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), and the Human Protein Atlas, we analyzed PLEK2 expression in both cancerous and normal tissues, revealing significant overexpression of PLEK2 in various cancers at the mRNA and protein levels. Single-cell RNA sequencing further indicated predominant expression of PLEK2 in tumor cells and macrophages within the tumor microenvironment. Survival analysis demonstrated that elevated PLEK2 expression correlated with poor prognosis in specific cancers, though its impact varied across cancer types. Functional assays showed that PLEK2 knockdown inhibited proliferation and migration in human cancer cell lines. In vivo studies using a Lewis lung carcinoma (LLC) model confirmed that PLEK2 knockdown suppressed tumor growth and enhanced the efficacy of PD-1 immunotherapy. Mechanistically, PLEK2 knockdown was associated with reduced AKT pathway activation, diminished tumor-associated macrophage infiltration, and increased CD8 T cell presence. Compounds like Navitoclax were also identified as potential PLEK2 inhibitors. In conclusion, PLEK2 played a multifaceted role in cancer progression and immune response modulation. Targeting PLEK2 might suppress tumor growth and overcome immunotherapy resistance, offering a promising biomarker and therapeutic target to improve cancer treatment outcomes.
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http://dx.doi.org/10.1186/s43556-024-00225-8 | DOI Listing |
Front Med (Lausanne)
December 2024
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Background: Uveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been reported. Through this study, we hope to explore the effect of PLEK2 on the prognosis of UVM patients and to discover the potential functional role and intrinsic mechanism of PLEK2.
View Article and Find Full Text PDFMol Biomed
November 2024
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Mol Cell Biochem
August 2024
Division of Pancreatic Surgery, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, China.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis primarily due to metastasis. Accumulating evidence suggests that PLEK2 acts as an oncogene in various tumors. This study aimed to investigate the effects of PLEK2 on PDAC.
View Article and Find Full Text PDFBMC Genomics
August 2024
Shaanxi Key Laboratory for Network Computing and Security Technology, School of Computer Science and Engineering, Xi'an University of Technology, Xi'an, Shaanxi, 710048, China.
Am J Pathol
October 2024
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois. Electronic address:
Phosphoinositide 3-kinase (PI3K)-AKT and androgen receptor (AR) pathways are commonly activated in prostate cancers. Their reciprocal regulation makes advanced prostate cancers difficult to treat. The current study shows that pleckstrin-2 (PLEK2), a proto-oncoprotein involved in the activation and stabilization of AKT, connects these two pathways.
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