Localization of cortactin is associated with colorectal cancer development

Hirakawa, Hiroshi; Shibata, Kenichiro; Nakayama, Toshiyuki

doi:10.3892/ijo_00000444

Cited by 33 publications

(31 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the apparent induction of CTTN in DTC may be via gene amplification, or other gene regulatory mechanisms. Notwithstanding this, CTTN overexpression has been extensively linked to invasive cancers, including melanoma, colorectal cancer, and glioblastoma (8, 29, 30). Future studies will need to determine whether intratumoral heterogeneity stemming from genetic and nongenetic variability influences the expression and colocalization of CTTN and PBF.…”

Section: Discussionmentioning

confidence: 99%

Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin

Watkins

Imruetaicharoenchoke

Read

et al. 2016

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

Context:Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates.Objective:The proto-oncogene PTTG1-binding factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumor aggressiveness. This study aimed to understand the role of PBF in tumor cell invasion and identify possible routes to inhibit its action.Design, Setting, Patients, and Interventions:Thyroid, breast, and colorectal cells were transfected with PBF and cultured for in vitro analysis. PBF and cortactin (CTTN) expression was determined in differentiated thyroid cancer and The Cancer Genome Atlas RNA-seq data.Primary Outcome Measure:Pro-invasive effects of PBF were evaluated by 2D Boyden chamber, 3D organotypic, and proximity ligation assays.Results:Our study identified that PBF and CTTN physically interact and co-localize, and that this occurs at the cell periphery, particularly at the leading edge of migrating cancer cells. Critically, PBF induces potent cellular invasion and migration in thyroid and breast cancer cells, which is entirely abrogated in the absence of CTTN. Importantly, we found that CTTN is over-expressed in differentiated thyroid cancer, particularly in patients with regional lymph node metastasis, which significantly correlates with elevated PBF expression. Mutation of PBF (Y174A) or pharmacological intervention modulates the PBF: CTTN interaction and attenuates the invasive properties of cancer cells.Conclusion:Our results demonstrate a unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration, as well as identify a new targetable interaction to block tumor cell movement.

show abstract

Section: Discussionmentioning

confidence: 99%

Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin

Watkins

Imruetaicharoenchoke

Read

et al. 2016

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

show abstract

“…During EMT, ZO-1 relocates from the adhesion membrane complexes to the cytoplasm and then to the nucleus, depending on the degree of differentiation and migration of the cell (Polette et al, 2007). ZO-1 is involved in the EMT process in colorectal and bile duct cancers, but has not yet been linked to EMT in HNSCC (Hirakawa et al, 2009;Nemeth et al, 2009).…”

Section: Future Directionsmentioning

confidence: 99%

Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma

et al. 2012

View full text Add to dashboard Cite

An understanding of the process by which tumor cells destroy the basement membrane of the surface epithelium, invade, and metastasize is essential to the development of novel treatment of head and neck squamous cell carcinoma (HNSCC). In recent years, there has been increased interest in the role of epithelial-mesenchymal transition (EMT) in invasion. EMT is a process that describes the development of motile, mesenchymal-like cells from non-motile parent epithelial cells. There are 3 known types of EMT that mediate development, wound healing, and carcinogenesis. This review summarizes studies of known EMT biomarkers in the context of HNSCC progression. The biomarkers discussed come from a wide range of proteins, including cell-surface proteins (E-cadherin, N-cadherin, and Integrins), cytoskeletal proteins (α-Smooth Muscle Actin, Vimentin, and β-catenin), extracellular matrix proteins (Collagens, Fibronectin, and Laminin), and transcription factors (SNAIL1, SNAIL2, TWIST, and LEF-1). Overall, the findings of these studies suggest that EMT mediates HNSCC progression. The mechanistic role of the EMT markers that have been associated with HNSCC should be more clearly defined if new anti-HNSCC therapies to block EMT progression are to be developed.KEY WORDS: disease progression, extracellular matrix, oral pathology, neoplasm invasiveness, biological markers, head and neck neoplasms.

show abstract

“…The cortactin SH3 domain interacts with the adhesioncomplex protein zona occludens protein 1 (ZO-1) (Hirakawa et al, 2009;Katsube et al, 1998). Cortactin has also been shown to act downstream of E-cadherin activated by Src kinase and is required for actin polymerization at these cell-cell adhesions (Helwani et al, 2004;Ren et al, 2009).…”

Section: Sh3-domain-binding Partners Regulate Cellular Processesmentioning

confidence: 99%

“…Amplification of the gene that encodes cortactin (CTTN) and the resulting overexpression of cortactin protein have been observed in 15% of primary metastatic breast carcinomas and in nearly 30% of head and neck squamous cell carcinomas (Akervall et al, 1995;Buday and Downward, 2007). Overexpression of cortactin has also been linked to invasive cancers, including melanoma, colorectal cancer and glioblastoma, making cortactin an important biomarker for invasive cancers (Hirakawa et al, 2009;Kirkbride et al, 2011;Rothschild et al, 2006;Weaver, 2008;Xu et al, 2010).…”

mentioning

confidence: 99%