FAK Signaling in Neoplastic Disorders

Mon, Naing Naing; Ito, Satoko; Senga, Takeshi; Hamaguchi, Michinari

doi:10.1196/annals.1377.019

Cited by 61 publications

(46 citation statements)

References 79 publications

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“…We also show here that MMP-2 is able to promote cell invasion in SCC cells. Previous studies have supported a role for FAK in MMP-2 secretion in response to environmental factors (Sein et al, 2000;Zhang et al, 2002;Mon et al, 2006b). Our studies show that FAK is implicated in MMP-2 gene expression leading to increased MMP-2 secretion in SCC cells.…”

Section: Discussionsupporting

confidence: 82%

“…In addition, transient overexpression of FAK in SCC cells increases cell invasion. Several reports have shown that FAK can regulate cell invasion not only by regulation of cell migration but also by the modulation of matrix metalloproteinases that degrade extracellular matrix barriers (Hsia et al, 2003;Mon et al, 2006b). We found that MMP-2 and MMP-9 gene expression were greatly reduced by FRNK expression in SCC40 cells.…”

Section: Discussionmentioning

confidence: 56%

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Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

et al. 2008

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Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies. Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer, comprising B50% of all malignancies in some developing nations. HNSCC is associated with severe disease-and treatment-related morbidity and has a 5-year survival rate of B50%. This survival rate has remained largely unchanged in the past three decades (Sankaranarayanan et al, 1998;Gonzalez-Botas and Vazquez Barro, 2006). A major determinant of the lethal progression of HNSCC is the spreading of the malignant cells to regional lymph nodes which represents a major prognostic indicator (Forastiere et al, 2001). Thus, attempts to identify the genes involved in metastasis are pivotal for the early prediction of HNSCC behaviour and development of novel molecular therapies. However, the identities of molecular alterations that endow cancer cells with these metastatic functions are largely unknown.The process of metastasis consists of sequential and selective steps including proliferation, motility, invasion, loss of cell -cell and cell -matrix adhesion, and remodelling of the extracellular matrix. A key factor involved in the control of cellextracellular matrix interactions is focal adhesion kinase (FAK), an intracellular tyrosine kinase protein that is localised to cellular focal contact sites (Schaller et al, 1992). Initially, phosphorylation of FAK occurs on its major autophosphorylation site, Tyr 397 . Phosphorylation of this tyrosine initiates a cascade of signal transdu...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 56%

Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

et al. 2008

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“…Previous studies have indicated that Src and FAK are related to cancer progression and invasion (32)(33)(34). Elevated Src expression has been observed in different types of cancer, including colon, breast, pancreatic and gastric cancer (27).…”

Section: A B C Dmentioning

confidence: 99%

Interleukin-1β activates focal adhesion kinase and Src to induce matrix metalloproteinase-9 production and invasion of MCF-7 breast cancer cells

2016

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Abstract. Interleukin-1β (IL-1b) is a pleiotropic cytokine that is important in tumor progression and invasion. Matrix metalloproteinase-9 (MMP-9), which is a secreted matrix-degrading enzyme, is one of the key regulators of tumor invasion and metastasis. The current report indicated that IL-1b promotes MMP-9 production and cell invasion in non-metastatic MCF-7 breast cancer cells. IL-1b activated focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase Src (Src). Moreover, inhibiting the Src/FAK pathway reduced the IL-1b-induced production of MMP-9 and cell invasion. To investigate the functional role of FAK in MMP-9 production cell lines expressing mutant FAK in FAK knock-out mouse fibroblasts were generated. In wild-type FAK-expressing cells, MMP-9 production was induced by IL-1b stimulation. By contrast, IL-1b-induced MMP-9 production was abrogated in FAK knock-out, FAK Y397F, FAK Y925F, and kinase dead mutant-expressing cells. Therefore the results of the current study indicate that FAK and Src kinases are activated by IL-1b and play a critical role in MMP-9 production and tumor cell invasion.

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“…Pro-MMPs lie dormant within the ECM and are activated by various signals (Murphy et al, 1999;Davidson et al, 2002;Tsuruda et al, 2004;Nagase et al, 2006;Amalinei et al, 2007;Ra and 2008). Misregulation of MMP activity contributes to multiple diseases (metastatic carcinoma, cardiovascular disease, rheumatoid arthritis, osteoarthritis, oral diseases) and is also implicated in preterm labor (Davidson et al, 2002;Abraham et al, 2005;Hofmann et al, 2005;Vadillo-Ortega and Estrada-Gutierrez, 2005;Lemaitre and D'Armiento, 2006;Liu et al, 2006;Mon et al, 2006;Cockle et al, 2007). The dynamic interaction between ECM synthesis/ assembly and degradation via MMPs is an exquisite balancing act that mediates both embryonic development and tissue homeostasis.…”

Section: Extracellular Matrix Proteinsmentioning

confidence: 99%

Dynamic interactions between cells and their extracellular matrix mediate embryonic development

Goody

Henry

2010

Molecular Reproduction Devel

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SUMMARYCells and their surrounding extracellular matrix microenvironment interact throughout all stages of life. Understanding the continuously changing scope of cell-matrix interactions in vivo is crucial to garner insights into both congenital birth defects and disease progression. A current challenge in the field of developmental biology is to adapt in vitro tools and rapidly evolving imaging technology to study cell-matrix interactions in a complex 4-D environment. In this review, we highlight the dynamic modulation of cell-matrix interactions during development. We propose that individual cell-matrix adhesion proteins are best considered as complex proteins that can play multiple, often seemingly contradictory roles, depending upon the context of the microenvironment. In addition, cell-matrix proteins can also exert different short versus long term effects. It is thus important to consider cell behavior in light of the microenvironment because of the constant and dynamic reciprocal interactions occurring between them. Finally, we suggest that analysis of cell-matrix interactions at multiple levels (molecules, cells, tissues) in vivo is critical for an integrated understanding because different information can be acquired from all size scales.Mol.

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FAK Signaling in Neoplastic Disorders

Cited by 61 publications

References 79 publications

Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

Interleukin-1β activates focal adhesion kinase and Src to induce matrix metalloproteinase-9 production and invasion of MCF-7 breast cancer cells

Dynamic interactions between cells and their extracellular matrix mediate embryonic development

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