ArticleMolecular and cellular biology2010
Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle progression in 11q13-amplified head and neck squamous cell carcinoma cells.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Inclusion of JNK-independent drugs within multiagent chemotherapy improves response in relapsed high-risk neuroblastoma.Science advances · 2025Article
- Activation of CAMK2 by pseudokinase PEAK1 represents a targetable pathway in triple negative breast cancer.Nature communications · 2025Article
- Enzyme-independent role of EZH2 in regulating cell cycle progression via the SKP2-KIP/CIP pathway.Scientific reports · 2024Article
- Prognostic impact of cortactin in patients with hypopharyngeal cancer and its role for tegafur-uracil maintenance after adjuvant chemoradiotherapy.American journal of cancer research · 2023Article
- The upregulation of stromal antigen 3 expression suppresses the phenotypic hallmarks of hepatocellular carcinoma through the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways.BMC gastroenterology · 2022Article
- Crumbs3 is expressed in oral squamous cell carcinomas and promotes cell migration and proliferation by affecting RhoA activity.Oncology letters · 2022Article
- Profiling the expression of pro-metastatic genes in association with the clinicopathological features of primary breast cancer.Cancer cell international · 2021Article
- The HBx-CTTN interaction promotes cell proliferation and migration of hepatocellular carcinoma via CREB1.Cell death & disease · 2019Article
- In search of the altering salivary proteome in metastatic breast and ovarian cancers.FASEB bioAdvances · 2019Article
- Homo- and Heterotypic Association Regulates Signaling by the SgK269/PEAK1 and SgK223 Pseudokinases.The Journal of biological chemistry · 2016Article
- Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1.Scientific reports · 2016Article
- Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility.Scientific reports · 2016Article
- The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling.Molecular cancer · 2015Article
- VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells.Biology open · 2015Article
- Cortactin in cell migration and cancer at a glance.Journal of cell science · 2012Review
- Cortactin: a multifunctional regulator of cellular invasiveness.Cell adhesion & migrationReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) downstream of cortactin were confirmed by the transient knockdown of each CDKI by specific small interfering RNAs, which led to partial rescue of cell cycle progression. Interestingly, FaDu cells with reduced cortactin levels also exhibited a significant diminution in RhoA expression and activity, together with decreased expression of Skp2, a critical component of the SCF ubiquitin ligase that targets p27(Kip1) and p57(Kip2) for degradation. Transient knockdown of RhoA in FaDu cells decreased expression of Skp2, enhanced the level of Cip/Kip CDKIs, and attenuated S-phase entry. These findings identify a novel mechanism for regulation of proliferation in 11q13-amplified HNSCC cells, in which overexpressed cortactin acts via RhoA to decrease expression of Cip/Kip CDKIs, and highlight Skp2 as a downstream effector for RhoA in this process.
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