ArticleThe Journal of clinical investigation2014
Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 131 citations in OpenAlex.
- Inferring Phenotypes of Single Cells Based on the Expression Profiles of Phenotype-Associated Marker Genes in Bulks and Single Cells.Interdisciplinary sciences, computational life sciences · 2026Article
- Integrated single-cell and spatial transcriptomic profiling decodes lineage plasticity and immune microenvironment remodeling in prostate cancer progression.Molecular cancer · 2026Article
- 3D collagen high-throughput screen identifies drugs that induce epithelial polarity and enhance chemotherapy response in colorectal cancer.Communications biology · 2025Article
- CDH3 promotes the progression of lung adenocarcinoma through driving epithelial-mesenchymal transition progress.Journal of translational medicine · 2025Article
- PLAC8 Expression Regulates Trophoblast Invasion and Conversion into an Endothelial Phenotype (eEVT).International journal of molecular sciences · 2025Article
- Article
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DUSP6 regulates Notch1 signalling in colorectal cancer.Nature communications · 2024Article
- Multiplex Genome Editing of Human Pluripotent Stem Cells Using Cpf1.Bio-protocol · 2024Article
- The Roles of RAC1 and RAC1B in Colorectal Cancer and Their Potential Contribution to Cetuximab Resistance.Cancers · 2024Review
- Applicability of Spatial Technology in Cancer Research.Cancer research and treatment · 2024Review
- Ontogenetically distinct neutrophils differ in function and transcriptional profile in zebrafish.Nature communications · 2023Article
- PLAC8 contributes to the malignant behaviors of cervical cancer cells by activating the SOX4-mediated AKT pathway.Histochemistry and cell biology · 2023Article
- Multiplex Immunofluorescence: A Powerful Tool in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Investigation of Underlying Biological Association and Targets between Rejection of Renal Transplant and Renal Cancer.International journal of genomics · 2023Article
- PLAC8 is an innovative biomarker for immunotherapy participating in remodeling the immune microenvironment of renal clear cell carcinoma.Frontiers in oncology · 2023Article
- MicroRNA 133A Regulates Cell Proliferation, Cell Migration, and Apoptosis in Colorectal Cancer by Suppressing CDH3 Expression.Journal of Cancer · 2023Article
- Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer.Journal for immunotherapy of cancer · 2022Article
- Long noncoding RNA GK-IT1 promotes esophageal squamous cell carcinoma by regulating MAPK1 phosphorylation.Cancer medicine · 2022Article
- Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors.Cell communication and signaling : CCS · 2022Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The epithelial-to-mesenchymal transition (EMT) transcriptional program is characterized by repression of E-cadherin (CDH1) and induction of N-cadherin (CDH2), and mesenchymal genes like vimentin (VIM). Placenta-specific 8 (PLAC8) has been implicated in colon cancer; however, how PLAC8 contributes to disease is unknown, and endogenous PLAC8 protein has not been studied. We analyzed zebrafish and human tissues and found that endogenous PLAC8 localizes to the apical domain of differentiated intestinal epithelium. Colon cancer cells with elevated PLAC8 levels exhibited EMT features, including increased expression of VIM and zinc finger E-box binding homeobox 1 (ZEB1), aberrant cell motility, and increased invasiveness. In contrast to classical EMT, PLAC8 overexpression reduced cell surface CDH1 and upregulated P-cadherin (CDH3) without affecting CDH2 expression. PLAC8-induced EMT was linked to increased phosphorylated ERK2 (p-ERK2), and ERK2 knockdown restored cell surface CDH1 and suppressed CDH3, VIM, and ZEB1 upregulation. In vitro, PLAC8 directly bound and inactivated the ERK2 phosphatase DUSP6, thereby increasing p-ERK2. In a murine xenograft model, knockdown of endogenous PLAC8 in colon cancer cells resulted in smaller tumors, reduced local invasion, and decreased p-ERK2. Using MultiOmyx, a multiplex immunofluorescence-based methodology, we observed coexpression of cytosolic PLAC8, CDH3, and VIM at the leading edge of a human colorectal tumor, supporting a role for PLAC8 in cancer invasion in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.