ArticlePloS one2013
p16 Stimulates CDC42-dependent migration of hepatocellular carcinoma cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Pooled it
- A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers.Disease models & mechanisms · 2022Article
- Loss of ARF/INK4A Promotes Liver Progenitor Cell Transformation Toward Tumorigenicity Supporting Their Role in Hepatocarcinogenesis.Gene expression · 2020Article
- Article
- Targeting P16INK4A in uterine serous carcinoma through inhibition of histone demethylation.Oncology reports · 2019Article
- ALDH1 as a prognostic marker for lymph node metastasis in OSCC.Biomedical reports · 2018Article
- Dual role for p16 in the metastasis process of HPV positive head and neck cancers.Molecular cancer · 2017Article
- C-terminal binding protein-2 promotes cell proliferation and migration in breast cancer via suppression of p16INK4A.Oncotarget · 2017Article
- A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination.Oncogene · 2016Article
- Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin.Nature communications · 2016Article
- Rho GTPases RhoA and Rac1 mediate effects of dietary folate on metastatic potential of A549 cancer cells through the control of cofilin phosphorylation.The Journal of biological chemistry · 2014Article
- Rac1 as a potential therapeutic target for chemo-radioresistant head and neck squamous cell carcinomas (HNSCC).British journal of cancer · 2014Article
- HBx inhibits CYP2E1 gene expression via downregulating HNF4α in human hepatoma cells.PloS one · 2014Article
- The other side of the coin: the tumor-suppressive aspect of oncogenes and the oncogenic aspect of tumor-suppressive genes, such as those along the CCND-CDK4/6-RB axis.Cell cycle (Georgetown, Tex.) · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Tumor dissemination to the extra-hepatic region of the portal vein, lymph nodes, lungs or bones contributes to the high mortality seen in HCC; yet, the molecular mechanisms responsible for HCC metastasis remain unclear. Prior studies have suggested a potential link between accumulated cytoplasm-localized p16 and tumor progression. Here we report that p16 enhances metastasis-associated phenotypes in HCC cells - ectopic p16 expression increased cell migration in vitro, and lung colonization after intravenous injection, whereas knockdown of endogenous p16 reduced cell migration. Interestingly, analysis of p16 mutants indicated that the Cdk4 interaction domain is required for stimulation of HCC cell migration; however, knockdown of Cdk4 and Cdk6 showed that these proteins are dispensable for this phenomenon. Intriguingly, we found that in p16-positive HCC samples, p16 protein is predominantly localized in the cytoplasm. In addition, we identified a potential role for nuclear-cytoplasmic shuttling in p16-stimulated migration, consistent with the predominantly cytoplasmic localization of p16 in IHC-positive HCC samples. Finally, we determined that p16-stimulated cell migration requires the Cdc42 GTPase. Our results demonstrate for the first time a pro-migratory role for p16, and suggest a potential mechanism for the observed association between cytoplasmic p16 and tumor progression in diverse tumor types.
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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.