ArticleMolecular cancer research : MCR2012
Constitutive K-RasG12D activation of ERK2 specifically regulates 3D invasion of human pancreatic cancer cells via MMP-1.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- Shaping epithelial tissues by stem cell mechanics in development and cancer.Nature reviews. Molecular cell biology · 2025Review
- Invadopodia in cancer metastasis: dynamics, regulation, and targeted therapies.Journal of translational medicine · 2025Review
- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
- Tumor-suppressive miR-29c binds to MAPK1 inhibiting the ERK/MAPK pathway in pancreatic cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation.Chinese medicine · 2021Article
- SWI/SNF complex alterations as a biomarker of immunotherapy efficacy in pancreatic cancer.JCI insight · 2021Article
- Tissue-Engineering the Fibrous Pancreatic Tumour Stroma Capsule in 3D Tumouroids to Demonstrate Paclitaxel Response.International journal of molecular sciences · 2021Article
- Rigidity controls human desmoplastic matrix anisotropy to enable pancreatic cancer cell spread via extracellular signal-regulated kinase 2.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- CCN6-mediated MMP-9 activation enhances metastatic potential of human chondrosarcoma.Cell death & disease · 2018Article
- A novel tricarbonylmethane agent (CMC2.24) reduces human pancreatic tumor growth in mice by targeting Ras.Molecular carcinogenesis · 2018Article
- Signaling pathways and mesenchymal transition in pediatric high-grade glioma.Cellular and molecular life sciences : CMLS · 2018Review
- MiR-22 suppresses epithelial-mesenchymal transition in bladder cancer by inhibiting Snail and MAPK1/Slug/vimentin feedback loop.Cell death & disease · 2018Article
- Invadosomes are coming: new insights into function and disease relevance.The FEBS journal · 2018Review
- Review
- Force-dependent breaching of the basement membrane.Matrix biology : journal of the International Society for Matrix Biology · 2017Review
- Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway.Oncology letters · 2016Article
- Modeling pancreatic cancer with organoids.Trends in cancer · 2016Article
- ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?Frontiers in cell and developmental biology · 2016Review
- Soluble Expression of Bladder Cancer Biomarker Matrix Metalloproteinase 1.Journal of clinical laboratory analysis · 2015Article
- Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer.Trends in biotechnology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinomas (PDAC) are highly invasive and metastatic neoplasms commonly unresponsive to current drug therapy. Overwhelmingly, PDAC harbors early constitutive, oncogenic mutations in K-Ras(G12D) that exist prior to invasion. Histologic and genetic analyses of human PDAC biopsies also exhibit increased expression of extracellular signal-regulated kinase (ERK) 1/2 and proinvasive matrix metalloproteinases (MMP), indicators of poor prognosis. However, the distinct molecular mechanisms necessary for K-Ras/ERK1/2 signaling and its influence on MMP-directed stromal invasion in primary human pancreatic ductal epithelial cells (PDEC) have yet to be elucidated in three-dimensions. Expression of oncogenic K-Ras(G12D) alone in genetically defined PDECs reveals increased invadopodia and epithelial-to-mesenchymal transition markers, but only when cultured in a three-dimensional model incorporating a basement membrane analog. Activation of ERK2, but not ERK1, also occurs only in K-Ras(G12D)-mutated PDECs cultured in three-dimensions and is a necessary intracellular signaling event for invasion based upon pharmacologic and short hairpin RNA (shRNA) inhibition. Increased active invasion of K-Ras(G12D) PDECs through the basement membrane model is associated with a specific microarray gene expression signature and induction of MMP endopeptidases. Specifically, MMP-1 RNA, its secreted protein, and its proteolytic cleavage activity are amplified in K-Ras(G12D) PDECs when assayed by real-time quantitative PCR, ELISA, and fluorescence resonance energy transfer (FRET). Importantly, shRNA silencing of MMP-1 mimics ERK2 inhibition and disrupts active, vertical PDEC invasion. ERK2 isoform and MMP-1 targeting are shown to be viable strategies to attenuate invasion of K-Ras(G12D)-mutated human pancreatic cancer cells in a three-dimensional tumor microenvironment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.