Inhibitory role of focal adhesion kinase on anoikis in the lung cancer cell A549

Liu, Gaiyun; Meng, Xin; Jin, Yan; Bai, Jing; Zhao, Yilong; Cui, Xiaobo; Chen, Feng; Fu, Songbin

doi:10.1016/j.cellbi.2008.01.292

Cited by 51 publications

(44 citation statements)

References 20 publications

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“…Upon detachment, levels of phospho-FAK and phospho-Src decrease and promote anoikis. In malignant cells, phospho-FAK and phospho-Src fail to decrease after detachment and thereby promote resistance to anoikis [20,22,36,[38][39][40][41]. However, in RWPE-1 cells, after 1 week in suspension conditions, levels of phospho-Src were slightly increased in the ABHD4 knockdown cells compared to control.…”

Section: Discussionmentioning

confidence: 55%

A genome wide shRNA screen identifies α/β hydrolase domain containing 4 (ABHD4) as a novel regulator of anoikis resistance

et al. 2012

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Acquisition of resistance to anchorage dependant cell death, a process termed anoikis, is a requirement for cancer cell metastasis. However, the molecular determinants of anoikis resistance and sensitivity are poorly understood. To better understand resistance to anoikis we conducted a genome wide lentiviral shRNA screen to identify genes whose knockdown render anoikis-sensitive RWPE-1 prostate cells resistant to anoikis. RWPE-1 cells were infected with a pooled lentiviral shRNA library with 54,021 shRNA targeting 11,255 genes. After infection, an anoikis-resistant cell population was selected and shRNA sequences were amplified and sequenced. Thirty-four shRNA sequences reproducibly protected RWPE-1 cells from anoikis after culture under suspension conditions including the top validated hit, α/β hydrolase domain containing 4 (ABHD4). In validation studies, ABHD4 knockdown inhibited anoikis in RWPE-1 cells as well as anoikis sensitive NP69 nasopharyngeal and OVCAR3 ovarian cancer cells, while over-expression of the gene increased sensitivity. Induction of anoikis after ABHD4 knockdown was associated with cleavage of PARP and activation of caspases-3, but was independent in changes of FLIP, FAK and Src expression. Interestingly, induction of anoikis after ABHD4 knockdown was independent of the known role of ABHD4 in the anandamide synthesis pathway and the generation of glycerophospho-N-acyl ethanolamines. Thus, ABHD4 is a novel genetic regulator of anoikis sensitivity.

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Section: Discussionmentioning

confidence: 55%

A genome wide shRNA screen identifies α/β hydrolase domain containing 4 (ABHD4) as a novel regulator of anoikis resistance

et al. 2012

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“…Upon integrin ligation, focal adhesion-kinase (FAK) is phosphorylated and interacts with several proteins, many of which stimulate proliferation and cellular survival [29]. The loss of integrin engagement eliminates these signals, thus committing detached cells to anoikis [30].…”

Section: The Effects Of Saha and Trail On The Level Of Integrins And Fakmentioning

confidence: 99%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

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a b s t r a c t SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERaÀpositive MCF-7 and the ERaÀnegative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show that SAHA decreased the level of c-FLIP, thus favouring the interaction of TRAIL with the specific death receptors DR4 and DR5 and the consequent activation of caspase-8. These effects increased when the cells were treated with SAHA/TRAIL combination. Because z-IEDT-fmk, an inhibitor of caspase-8, prevented both the cleavage of the focal adhesion-kinase FAK and cell detachment, we suggest that activation of caspase-8 can be responsible for both the decrement of FAK and the consequent cell detachment. In addition, treatment with SAHA/TRAIL combination caused dissipation of DJ m , activation of caspase-3 and decrement of both phospho-EGFR and phospho-ERK1/2, a kinase which is involved in the phosphorylation of BimEL. Therefore, co-treatment also induced decrement of phospho-BimEL and a concomitant increase in the dephosphorylated form of BimEL, which plays an important role in the induction of anoikis.Our findings suggest the potential application of SAHA in combination with TRAIL in clinical trials for breast cancer.

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“…3A). Such increase of Y397 phosphorylation in suspension culture condition of cancer cells was reported previously (10,11). In contrast, Y397 phosphorylation of FAK in 293T-STEAP4 cells was not increased, but rather decreased in suspension culture (Fig.…”

Section: Steap4 Regulates Y397 Phosphorylation Of Fakmentioning

confidence: 48%

STEAP4 regulates focal adhesion kinase activation and CpG motifs within STEAP4 promoter region are frequently methylated in DU145, human androgen-independent prostate cancer cells

Tamura

Chiba²

2009

Int J Mol Med

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Abstract. The possible roles of STEAP4 in cancer progression have not been reported. In this study, we report that STEAP4 expression is able to inhibit anchorage-independent cell growth. We also demonstrate that STEAP4 associates with focal adhesion kinase (FAK) and regulate the activity of FAK through Y397 phosphorylation. Furthermore, we show that CpG sequences in STEAP4 promoter region were frequently methylated in DU145, androgen-independent prostate cancer cells. Demethylation treatment induced STEAP4 expression in DU145, suggesting the possibility that STEAP4 expression in cancer cells is in part epigenetically regulated. Collectively, these data demonstrate a novel function of STEAP4 and that STEAP4 may play an important role in tumor malignancy.

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Inhibitory role of focal adhesion kinase on anoikis in the lung cancer cell A549

Cited by 51 publications

References 20 publications

A genome wide shRNA screen identifies α/β hydrolase domain containing 4 (ABHD4) as a novel regulator of anoikis resistance

A genome wide shRNA screen identifies α/β hydrolase domain containing 4 (ABHD4) as a novel regulator of anoikis resistance

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

STEAP4 regulates focal adhesion kinase activation and CpG motifs within STEAP4 promoter region are frequently methylated in DU145, human androgen-independent prostate cancer cells

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