Survivin expression by metastatic melanoma predicts poor disease outcome in patients receiving adjuvant polyvalent vaccine

Takeuchi, Hiroya; Morton, Donald L.; Elashoff, David; Hoon, Dave S.B.

doi:10.1002/ijc.21267

Cited by 71 publications

(65 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Elevated levels of microphthalmia associated transcription factor (MITF) which directly upregulates Bcl-2 expression has been linked to melanoma progression 67 . The inhibitor of Fasassociated apoptosis, FLIP (FLICE (FADD-like interleukin-1 beta-converting enzyme) inhibitory protein), has also been seen to be upregulated in human melanoma 68 and a high expression level of the inhibitor of apoptosis protein (IAP), survivin, has been linked to poor prognosis for patients with metastatic melanoma and a decreased response to immunotherapy 69 .…”

Section: Chemoresistance and Treatment In Malignant Melanomamentioning

confidence: 99%

“…Indeed in late stage metastatic melanoma NFB also upregulates pro-survival molecules such as FLIP, survivin and some pro-survival Bcl-2 family members 68,69,235 . The switch between the pro-apoptotic and pro-survival functions of NFB comes from the result of other chemokines and growth factors activating the pathways and the expression levels of various proteins involved in the pathways.…”

Section: The Nfb Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

Role of the pro-survival molecule Bfl-1 in melanoma

Hind

Carter

Harris

et al. 2015

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Melanoma, the cancer derived from the melanocytes of the skin, is becoming an ever more common cancer in the ageing population of the developed world and displays an intrinsic resistance to current therapies. This chemo resistance makes metastatic melanoma an extremely difficult cancer to treat leading to a 5 year survival rate of just 20%. As such, it is important to unearth new potential drug targets to increase the prospects for melanoma patients.Bfl-1 is a pro-survival protein of the Bcl-2 family of apoptosis regulating proteins. It has been found to be over-expressed in a small subset of chemo resistant tumours, including melanoma. Accordingly, I characterised the molecule in melanoma cells and determined its role in protecting these cells from chemotherapy-induced apoptosis. I elucidated the expression profile and half-lives of the protein and mRNA across a panel of melanoma cell-lines and healthy melanocytes. I also confirmed, using pathway specific inhibitors, that Bfl-1 was transcriptionally regulated by the NFB pathway and concluded through pulsechase experiments that Bfl-1 protein was degraded, at least in part, by the proteasome. Subcellular fractionation and indirect immunofluorescence techniques elucidated that Bfl-1 was located mostly at the mitochondria in both resting and apoptotic cells, with a diffuse level present throughout the cytoplasm. As well as characterising the protein in both melanoma cells and healthy primary melanocytes, I determined its role in the resistance of these cells to apoptosis. Over-expressed Bfl-1 was found to protect melanoma cells from apoptosis caused by a range of chemotherapeutic agents in A375 melanoma cells, which naturally expressed very low levels of Bfl-1. Further, knock down of Bfl-1 using siRNA technology in melanoma cells revealed the dependence of these cells on Bfl-1 for their resistance to certain chemotherapeutic agents currently used in melanoma treatment, including the MEK inhibitor PD901. All together, this research contributes to our understanding of Bfl-1 and highlights it as a potentially important therapeutic target in metastatic melanoma.

show abstract

Section: Chemoresistance and Treatment In Malignant Melanomamentioning

confidence: 99%

Section: The Nfb Pathwaymentioning

confidence: 99%

Role of the pro-survival molecule Bfl-1 in melanoma

Hind

Carter

Harris

et al. 2015

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

show abstract

“…Highly expressed survivin has been found in a growing number of carcinomas, such as colorectal adenocarcinoma, esophageal carcinoma, non-small cell lung carcinoma, pancreatic cancer, and melanoma, and demonstrated to be associated with biologically aggressive characteristics including unfavorable prognosis in some tumors (Kawasaki et al, 1998;Kato et al, 2001;Kren et al, 2004;Abd El-Hameed, 2005;Lee et al, 2005;Shinohara et al, 2005;Takeuchi et al, 2005). In addition, the high Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells prevalence of survivin is also found in the premalignant lesions of skin carcinoma and uterine carcinoma (Grossman et al, 1999;Kim et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells

Zhang²,

Gao³

et al. 2006

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…The toxicity in the control groups and in the group patient samples. 11,23 Expression of survivin, livin and XIAP have been correlated with drug resistance, progression and reduced survival 12,23,24 and nuclear expression of survivin has been suggested as an prognostic factor. 11 The data presented in this study also imply that IAP expression is frequent and concomitant in melanoma, and the expression level tend to be elevated compared to normal cells.…”

confidence: 99%