Focal adhesion kinase serves as a marker of cervical lymph node metastasis and is a potential therapeutic target in tongue cancer

Jiang, Hongbing; Liu, Laikui; Ye, Jinhai; Liu, Hualian; Xing, Shuzhong; Wu, Yunong

doi:10.1007/s00432-010-0780-4

Cited by 25 publications

(28 citation statements)

References 30 publications

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“…Similarly, a study in 80 OSCC archival specimens showed that FAK expression was found in all tumors and 55 of them (69%) displayed a moderate to high expression. 7 A separate study also reported that FAK is expressed in 60 of 67 OSCC tumors (90%) and 38 of them (57%) exhibit a moderate to high expression. 23 Compared with the intensive studies in FAK expression in OSCC, relatively few researches examined the levels of pY397 in benign and malignant oral lesions.…”

Section: Discussionmentioning

confidence: 90%

“…5 In OSCC cells, the expression of FAK in the primary or invasive OSCC tumors is higher than that in benign oral tissues, and modulation of FAK expression or activity regulates the invasive properties of OSCC cells. [6][7][8] However, the role of Y397 phosphorylation (pY397) in the FAK-promoted invasiveness in OSCC cells and its possible mechanism is mostly unknown.…”

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confidence: 99%

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Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

Yuan

2016

Laboratory Investigation

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Oral squamous cell carcinoma (OSCC) is a common cancer worldwide. Despite advances in diagnosis and therapy, treatment options for patients with metastatic OSCC are few, due in part to the limited understanding of the molecular events involved in the invasion and metastasis of OSCC. In this study, we investigated the expression of focal adhesion kinase (FAK) and its tyrosine 397 phosphorylation (pY397) in the tissue specimens of OSCC. The roles of pY397 in regulating the activities of Rac1 and cortactin and the invasive properties of OSCC cells were further determined. Results from immunohistochemical analyses in 9 benign, 19 premalignant, and 19 malignant oral tissues showed that the immunoreactivity of FAK was observed in 5 benign (56%), 19 premalignant (100%), and 18 malignant tissues (95%), whereas the immunoreactivity of pY397 was only found in 1 of 9 (11%) benign lesions but was observed in 9 premalignant (47%) and 12 malignant (63%) lesions. Compared with the low-invading SCC4 cells, the high-invading OECM-1 cells exhibited higher levels of FAK expression and pY397, correlating with higher levels of GTP-bound Rac1 and cortactin phosphorylation. Manipulation of FAK expression or Y397 phosphorylation in SCC4, FaDu, OECM-1, or HSC-3 cells regulated their Rac1 activities and invasive properties. Furthermore, treatment of NSC23766, a Rac1-specific inhibitor, in OECM-1 and HSC-3 cells led to reduced invasive properties. Nevertheless, knockdown of FAK expression or suppression of pY397 had no effect on the cortactin activity in OECM-1 cells. The data collectively suggest that pY397 plays critical roles in the FAK-promoted Rac1 activation and invasive properties in OSCC cells. Thus, the inhibition of FAK phosphorylation at Y397 or Rac1 activity can serve as a therapeutic strategy for treating patients with metastatic OSCC. Oral squamous cell carcinoma (OSCC) is the most common malignancy occurring in the oral cavity that usually arises from the buccal mucosa and tongue. During the tumor progression, OSCC cells gradually spread and invade to neighboring tissues, including the nasal cavity or the maxillary facial structures, and eventually metastasize to neck lymph nodes and distant organs. 1 Similar to other malignant diseases, tumor metastasis is a great challenge for the treatment of OSCC. This notion is supported by the fact that only 50% of diagnosed OSCC patients can survive for 5 years, and this is mainly because OSCC patients continue to die from tumor relapse at regional or distant sites. 2 Despite advances in diagnosis and therapy in past decades, the promising strategy for treating patients with metastatic OSCC is still underdeveloped, due in part to the limited understanding of the molecular events involved in invasion and metastasis of OSCC. The underlying molecular basis of OSCC metastasis deserves intensive study.Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase and functionally involves the regulatory processes of multiple cellular events, including adhesion, migration, invasion, prolifer...

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Section: Discussionmentioning

confidence: 90%

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confidence: 99%

Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

Yuan

2016

Laboratory Investigation

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“…As shown in Figure 4A and 4B, cells treated with 100 μM CoCl 2 significantly migrated faster (1.7 times in M139 cells and 1.2 times in M214 cells) than untreated cells in which their wounds had closed at 36 h for M139 and 16 h for M214 cells. A metastasis marker, pFAK (phosphorylated focal adhesion kinase (Jiang et al, 2010)) and LC3-II were determined in CCA cells treated with CoCl 2 using western blotting. As depicted in Figure 4C and 4D, the 100 μM CoCl 2 treated cells increased the levels of LC3-II and pFAK when compared with untreated cells.…”

Section: Cocl 2 Stabilized Hif-1α With Induction Of Autophagicresponsmentioning

confidence: 99%

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

Thongchot

Yongvanit²,

Loilome³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxicresponsive proteins (HIF-1α and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition (CoCl 2 treatment) was also tested regarding CCA cell functions. Our results showed that HIF-1α (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-1α (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-1α was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-1α (p=0.047) or co-expressed HIF-1α and BNIP3 (p=0.032) or HIF-1α and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with CoCl 2 showed an increase in HIF-1α, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.

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“…FAK overexpression has been associated with breast cancer lung metastasis (37,38), and FAK inhibitors have been introduced in novel therapeutic strategies (20,(39)(40)(41). An association between FAK overexpression and lymphatic metastasis has been identified in non-small-cell lung, oral squamous cell, esophageal, gastric, tongue, laryngeal and endometrial cancer by retrospective analysis of clinical samples (42)(43)(44)(45)(46)(47)(48)(49). Upregulation of FAK in the SKOV-3/LN403 cell line and clinical pathological specimens suggests that it may contribute to the high lymphatic metastaticity of the SKOV-3/LN403 cell line.…”

Section: Discussionmentioning

confidence: 99%

Identification of lymphatic metastasis-associated genes in a metastatic ovarian cancer cell line

Kang

Cai³

et al. 2015

Molecular Medicine Reports

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Abstract. Ovarian cancer (OC) is the gynecological malignancy with the highest rate of mortality, and lymphatic metastasis is a critical factor in disease recurrence and prognosis. In the current study, the SKOV-3/LN403 cell line, which has high potential for lymph node metastasis was established as a result of four rounds of selection from retroperitoneal lymph nodes following intraperitoneal injections of SKOV-3 ovarian adenocarcinoma cells. In comparison to the parental SKOV-3 cell line, SKOV-3/LN403 has a higher rate of proliferation, is more invasive and exhibits greater resistance to paclitaxel. Subsequently, a novel animal model of OC lymphatic metastasis was developed with SKOV-3/LN403 cells and a high incidence of positive metastatic lymph nodes, peritoneal dissemination and bloody ascites were observed, which mimicked the clinical outcome of patients with OC. Analysis of the gene expression profiles of SKOV-3 and SKOV-3/LN403 cells identified several genes and pathways that may be involved in lymphatic metastasis of OC. The induction of focal adhesion kinase expression provides a potential therapeutic target for OC lymphatic metastasis.

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Focal adhesion kinase serves as a marker of cervical lymph node metastasis and is a potential therapeutic target in tongue cancer

Abstract: These results suggest that FAK may serve as a marker of cervical lymph node metastasis of tongue cancer and that RNAi targeting FAK could serve as a potential therapeutic for the treatment of tongue cancer.

Cited by 25 publications

References 30 publications

Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

Identification of lymphatic metastasis-associated genes in a metastatic ovarian cancer cell line

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