ArticleOncotarget2015
The combinatorial activation of the PI3K and Ras/MAPK pathways is sufficient for aggressive tumor formation, while individual pathway activation supports cell persistence.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- AI-Guided Discovery of Oncogenic Signaling Crosstalk in Tumor Progression and Drug Resistance.Oncology research · 2026Review
- PI3K/Akt/mTOR pathway expression profiling reveals age- and subtype-specific molecular heterogeneity in the Nigerian breast cancer landscape.Frontiers in oncology · 2026Article
- Divergent oncogenic signaling and immune microenvironment changes in low-grade serous ovarian cancer patients undergoing intraperitoneal chemotherapy.NPJ precision oncology · 2025Article
- Disruption of P2Y2 Signaling Promotes Breast Tumor Cell Dissemination by Reducing ATP-Dependent Calcium Elevation and Actin Localization to Cell Junctions.International journal of molecular sciences · 2025Article
- Article
- Influence of recipient KRAS gene rs712 polymorphisms on the overall survival rate of hepatocellular carcinoma after hepatic transplantation.Clinical and experimental medicine · 2024Article
- LATS2 condensates organize signalosomes for Hippo pathway signal transduction.Nature chemical biology · 2024Article
- Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.Molecular cancer · 2024Review
- Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration.International journal of molecular sciences · 2022Article
- Polarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis.Nature communications · 2022Article
- Label-free cell tracking enables collective motion phenotyping in epithelial monolayers.iScience · 2022Article
- Article
- Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy.Molecular biomedicine · 2022Review
- Distinct roles of tumor associated mutations in collective cell migration.Scientific reports · 2021Article
- Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens.Nature biomedical engineering · 2019Article
- Oncosuppressor-Mutated Cells as a Liquid Biopsy Test for Cancer-Screening.Scientific reports · 2019Article
- MicroRNA-326 Functions as a Tumor Suppressor in Breast Cancer by Targeting ErbB/PI3K Signaling Pathway.Frontiers in oncology · 2019Article
- Emerging ways to treat breast cancer: will promises be met?Cellular oncology (Dordrecht, Netherlands) · 2018Review
- Effects of PTEN Loss and Activated KRAS Overexpression on Mechanical Properties of Breast Epithelial Cells.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A high proportion of human tumors maintain activation of both the PI3K and Ras/MAPK pathways. In basal-like breast cancer (BBC), PTEN expression is decreased/lost in over 50% of cases, leading to aberrant activation of the PI3K pathway. Additionally, BBC cell lines and tumor models have been shown to exhibit an oncogenic Ras-like gene transcriptional signature, indicating activation of the Ras/MAPK pathway. To directly test how the PI3K and Ras/MAPK pathways contribute to tumorigenesis, we deleted PTEN and activated KRas within non-tumorigenic MCF-10A breast cells. Neither individual mutation was sufficient to promote tumorigenesis, but the combination promoted robust tumor growth in mice. However, in vivo bioluminescence reveals that each mutation has the ability to promote a persistent phenotype. Inherent in the concept of tumor cell dormancy, a stage in which residual disease is present but remains asymptomatic, viable cells with each individual mutation can persist in vivo during a period of latency. The persistent cells were excised from the mice and showed increased levels of the cell cycle arrest proteins p21 and p27 compared to the aggressively growing PTEN-/-KRAS(G12V) cells. Additionally, when these persistent cells were placed into growth-promoting conditions, they were able to re-enter the cell cycle and proliferate. These results highlight the potential for either PTEN loss or KRAS activation to promote cell survival in vivo, and the unique ability of the combined mutations to yield rapid tumor growth. This could have important implications in determining recurrence risk and disease progression in tumor subtypes where these mutations are common.
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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.