B-RAF and PI-3 kinase signaling protect melanoma cells from anoikis

Boisvert-Adamo, Karen; Aplin, Andrew E.

doi:10.1038/sj.onc.1209493

Cited by 60 publications

(75 citation statements)

References 48 publications

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“…Bad-expressing cells replated onto fibronectin did not display enhanced cleaved caspase-3 staining (Figures 2b and c). In suspension, knockdown of B-RAF induced caspase-3 cleavage in approximately 60% of the LacZ control cells (Figures 2b and c), similar to the parental WM793 cells (Boisvert-Adamo and Aplin, 2006). Ectopic expression of either wild-type Bad or S75A Bad caused a fourfold increase in the percentage of cells staining positive for cleaved caspase-3 in the absence of B-RAF knockdown although not to the level of that achieved with B-RAF knockdown.…”

Section: Bad Expression and Phosphorylation Are Regulated By B-raf-mementioning

confidence: 61%

“…Therefore, this study describes mechanisms by which a common oncogene, B-RAF, promotes resistance to anoikis, a hallmark of malignant cancer cells. We have previously shown that mutant B-RAF protects melanoma cells from anoikis (Boisvert-Adamo and Aplin, 2006). To understand the mechanism underlying this effect, we initially analysed Bad, a BH3-only proapoptotic protein.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that mutant B-RAF protects human melanoma cells from anoikis (Boisvert-Adamo and Aplin, 2006). To understand the mechanisms underlying B-RAF effects on cell survival we initially analysed the Bcl-2 family protein, Bad, that is phosphorylated by RSK1 at the inhibitory serine-75 residue in a MEK-dependent manner in melanoma cells (Eisenmann et al, 2003).…”

Section: Bad Expression and Phosphorylation Are Regulated By B-raf-mementioning

confidence: 99%

“…Whole-cell lysates were prepared and processed as previously described (Boisvert-Adamo and Aplin, 2006). Chemiluminescence was detected using the Fluor-S Multi-Imager (Bio-Rad, Hercules, CA, USA) and quantitated using Quantity One software.…”

Section: Western Blottingmentioning

confidence: 99%

“…In our previous studies, we have shown that mutant B-RAF-harboring melanoma cells are susceptible to anoikis when B-RAF is depleted or MEK inhibited (Boisvert-Adamo and Aplin, 2006). Cell survival of B-RAF-depleted melanoma cells was restored by adhesion to fibronectin, which is a minor matrix component of the dermis.…”

Section: Introductionmentioning

confidence: 98%

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Mutant B-RAF mediates resistance to anoikis via Bad and Bim

Boisvert-Adamo

Aplin

2008

Oncogene

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Section: Bad Expression and Phosphorylation Are Regulated By B-raf-mementioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Bad Expression and Phosphorylation Are Regulated By B-raf-mementioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Mutant B-RAF mediates resistance to anoikis via Bad and Bim

Boisvert-Adamo

Aplin

2008

Oncogene

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Blood‐Lymphatic Integrated System with Heterogeneous Melanoma Spheroids via In‐Bath Three‐Dimensional Bioprinting for Modelling of Combinational Targeted Therapy

et al. 2022

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Although metastatic melanoma can be managed with chemotherapy, its heterogeneity and resistance to therapy remain poorly understood. In addition to the spread of melanoma in the bloodstream, melanoma‐stroma interaction and the lymphatic system play active roles in said heterogeneity and resistance, leading to its progression and metastasis. Reproducing the complexities of the melanoma microenvironment in vitro will help understanding its progression and enhance the translatability of potential cancer therapeutics. A blood‐lymphatic integrated system with heterogeneous melanoma spheroids (BLISH) using the in‐bath bioprinting process is developed. The process uniformly prints size‐controllable metastatic melanoma spheroids along with biomimetic blood and lymphatic vessels (LVs). The system reproduces hallmark events of metastatic melanoma, such as tumor stroma interaction, melanoma invasion, and intravasation. The application of the system to investigate the anticancer effect of combinational targeted therapy suggests that it can be used to study the pathophysiology of melanoma and improve the accuracy of drug response monitoring in skin cancer.

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Pathologic expression of MHC class II is driven by mitogen‐activated protein kinases

et al. 2007

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The class II transactivator (CIITA) is the master regulator of MHC class II molecules (MHC II). In melanoma, the MHC II are constitutively expressed due to an abnormal transcription of CIITA from its promoter III (pIII), and requires the presence of a 1-kb enhancer located upstream from this latter. Since mitogen-activated protein kinases (MAPK) have been shown to be activated in most melanomas, we sought to analyze their possible involvement in CIITA expression. Using chemical inhibitors and dominantnegative constructs of MAPK-ERK kinase (Mek1) and MAPK-JNK, we evidenced the inhibition of MHC II and CIITA expression in melanoma cell lines displaying activated MAPK. Transcriptional regulation by MAPK is known to involve the AP-1 transcription factor family. Sequence analysis revealed an AP-1-responsive motif in the enhancer of CIITA pIII at -5954/-5947 from the site of transcription initiation. Its mutagenesis reduced CIITA expression four-to fivefold in melanoma cell lines and alleviated the effect of dominant-negative constructs of the MAPK pathway. Together, our findings demonstrate that MAPK-ERK and MAPK-JNK are regulators of CIITA transcription in melanoma, and pinpoint an AP-1-responsive site in the CIITA gene pIII. This should have considerable impact on our understanding of the physio-pathologic expression of MHC II.

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B-RAF and PI-3 kinase signaling protect melanoma cells from anoikis

Cited by 60 publications

References 48 publications

Mutant B-RAF mediates resistance to anoikis via Bad and Bim

Mutant B-RAF mediates resistance to anoikis via Bad and Bim

Blood‐Lymphatic Integrated System with Heterogeneous Melanoma Spheroids via In‐Bath Three‐Dimensional Bioprinting for Modelling of Combinational Targeted Therapy

Pathologic expression of MHC class II is driven by mitogen‐activated protein kinases

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