ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 90 citations in OpenAlex.
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- Clinical Features, Molecular Biology, and the Metastatic Microenvironment in Lung Cancer Brain Metastases: Implications for Treatment Decisions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- TNFα activation of the PLEKHA5-FCRLA axis disturbs lipid metabolism, leading to the progression of cutaneous malignant melanoma.Lipids in health and disease · 2025Article
- Breaking boundaries: role of the brain barriers in metastatic process.Fluids and barriers of the CNS · 2025Review
- Single-cell transcriptomics and functional validation revealed PLEKHA5-L as a promoter of growth and migration in brain metastatic melanoma cells.Frontiers in oncology · 2025Article
- Vascular mimicry as a facilitator of melanoma brain metastasis.Cellular and molecular life sciences : CMLS · 2024Article
- Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma.JCO precision oncology · 2024Article
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- Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases.Journal for immunotherapy of cancer · 2023Article
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- Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments antitumor activity in melanoma.JCI insight · 2023Article
- Pan-cancer molecular subtypes of metastasis reveal distinct and evolving transcriptional programs.Cell reports. Medicine · 2023Article
- Proximity Labeling Reveals Spatial Regulation of the Anaphase-Promoting Complex/Cyclosome by a Microtubule Adaptor.ACS chemical biology · 2022Article
- Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma.Cellular and molecular life sciences : CMLS · 2022Article
- Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis.Cancer discovery · 2022Article
- Emerging Biomarkers for Diagnosis, Prevention and Treatment of Brain Metastases-From Biology to Clinical Utility.Diseases (Basel, Switzerland) · 2022Review
- Characterizing metastatic uveal melanoma patients who develop symptomatic brain metastases.Frontiers in oncology · 2022Article
- Blood-brain barrier and brain structural changes in lung cancer patients with non-brain metastases.Frontiers in oncology · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
purposeApproximately 40% of patients with metastatic melanoma develop brain metastases. Our purpose was to identify genes aberrantly expressed in melanoma that might be associated with propensity for brain homing. EXPERIMENTAL
designWe studied gene expression profiles in a cell line model of brain metastasis (cerebrotropic A375Br cells vs. parental A375P cells) and compared them with profiles of patients who developed early brain metastases and who did not. A tissue microarray containing 169 metastatic melanoma cases with variable time to brain metastasis was constructed to further study marker expression by quantitative immunofluorescence. An in vitro model of the blood brain barrier (BBB) was generated to evaluate potential mediators of brain metastases.
resultsPLEKHA5 was differentially expressed in both the A375 cell line model and patient samples subjected to gene expression profiling. At the protein level, by quantitative immunofluorescence, PLEKHA5 was associated with decreased brain metastasis-free survival. PLEKHA5 overexpression was not associated with other metastatic sites. Knockdown of PLEKHA5 decreases the viability of A375Br cells, inhibits BBB transmigration and invasion in vitro. Similar results were found with YUMUL cells, cultured from a patient with overwhelming brain metastases. PLEKHA5 knockdown did not affect the viability of A375P cells.
conclusionsPLEKHA5 expression in melanoma tumors was associated with early development of brain metastases. Inhibition of PLEKHA5 might decrease passage across the BBB and decrease proliferation and survival of melanoma cells both in the brain and in extracerebral sites.
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