Silencing of anti-apoptotic transmembrane protein lifeguard sensitizes solid tumor cell lines MCF-7 and SW872 to perifosine-induced cell death activation

Bucan, Vesna; Choi, Claudia; Lazaridis, Andrea; Vogt, Peter M.; Reimers, Kerstin

doi:10.3892/ol.2011.285

Cited by 8 publications

(10 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A year later, the same authors reported that FAIM2 down‐regulation enhanced sensitivity to an agonistic Fas antibody and to perifosine, an alkylphospholipid that induces apoptosis by inhibiting the AKT and phosphatidylinositol 3‐kinase pathway (Bucan et al . ). Recent studies described a new isoform of FAIM2, named FAIM2β, which lacks one of the transmembrane domains.…”

Section: Faim2mentioning

confidence: 97%

“…These data allowed them to hypothesize that FAIM2 participates in protecting breast cancer cells from apoptosis, conferring on them a more aggressive phenotype (Bucan et al 2010b). A year later, the same authors reported that FAIM2 down-regulation enhanced sensitivity to an agonistic Fas antibody and to perifosine, an alkylphospholipid that induces apoptosis by inhibiting the AKT and phosphatidylinositol 3-kinase pathway (Bucan et al 2011). Recent studies described a new isoform of FAIM2, named FAIM2b, which lacks one of the transmembrane domains.…”

Section: Faim2mentioning

confidence: 99%

“…Several studies were conducted in breast cancer models and described FAIM2 as an anti‐apoptotic protein that contributed to cancer progression (Bucan et al . ,b, ). Bucan et al .…”

Section: Faim2mentioning

confidence: 99%

See 2 more Smart Citations

Fas apoptosis inhibitory molecules: more than death‐receptor antagonists in the nervous system

Planells-Ferrer

Urresti

Coccia

et al. 2016

Journal of Neurochemistry

View full text Add to dashboard Cite

The importance of death receptor (DR) signaling in embryonic development and physiological homeostasis is well established, as is the existence of several molecules that modulate DRs function, among them Fas Apoptotis Inhibitory Molecules. Although FAIM1, FAIM2, and FAIM3 inhibit Fas-induced cell death, they are not structurally related, nor do they share expression patterns. Moreover, they inhibit apoptosis through completely different mechanisms. FAIM1 and FAIM2 protect neurons from DR-induced apoptosis and are involved in neurite outgrowth and neuronal plasticity. FAIM1 inhibits Fas ligand-and tumor necrosis factor alpha-induced apoptosis by direct interaction with Fas receptor and through the stabilization of levels of X-linked inhibitor of apoptosis protein, a potent anti-apoptotic protein that inhibits caspases. Low FAIM1 levels are found in Alzheimer's disease, thus sensitizing neurons to tumor necrosis factor alpha and prompting neuronal loss. FAIM2 protects from Fas by direct interaction with Fas receptor, as well as by modulating calcium release at the endoplasmic reticulum through interaction with Bcl-xL. Several studies prove the role of FAIM2 in diseases of the nervous system, such as ischemia, bacterial meningitis, and neuroblastoma. The less characterized member of the FAIM family is FAIM3, which is expressed in tissues of the digestive and urinary tracts, bone marrow and testes, and restricted to the cerebellum in the nervous system. FAIM3 protects against DR-induced apoptosis by inducing the expression of other DRantagonists such as CFLAR or through the interaction with the DR-adaptor protein Fas-associated via death domain. FAIM3 null mouse models reveal this protein as an important mediator of inflammatory autoimmune responses such as those triggered in autoimmune encephalomyelitis. Given the

show abstract

Section: Faim2mentioning

confidence: 97%

Section: Faim2mentioning

confidence: 99%

See 1 more Smart Citation

Fas apoptosis inhibitory molecules: more than death‐receptor antagonists in the nervous system

Planells-Ferrer

Urresti

Coccia

et al. 2016

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…In previous publications, it has been demonstrated that there is a correlation between the expression level of LFG and the increasing degree of malignity of breast cancer ( 5 ). Furthermore, it was shown that the effect of the alkyl phospholipid perifosine was reduced in cells expressing LFG ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

TRIM21, a negative modulator of LFG in breast carcinoma MDA-MB-231 cells in vitro

Müller¹,

Maurer²,

Reimers³

et al. 2015

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Lifeguard (LFG) is a transmembrane protein which is highly expressed in tissues of the hippocampus and the cerebellum, especially during postnatal development. This protein is responsible for the protection of neurons against Fas-induced apoptosis, and the same effect can be seen in tumor cells derived from mastocarcinoma. However, the molecular function of LFG and its regulation in the carcinogenesis of human breast cells remains to be elucidated. In the present study, we investigated the connection of the interaction of LFG within an array analysis of over 9,000 different proteins. Results showed an interaction between the proteins tripartite motif-containing 21 (TRIM21) and LFG and a negative regulatory effect of TRIM21 towards LFG on the protein level. Furthermore, Fas-induced apoptosis decreased upon the addition of TRIM21 to the cultured cells. These results revealed TRIM21 to be a negative modulator of LFG in cells of mastocarcinoma in vitro. For all analyses, MDA-MB-231 cells were used. The interaction of TRIM21 and LFG was analyzed by co-immunoprecipitation. To examine changes in regulatory processes, western blot analyses, real-time PCR, activity of apoptotic process and flow cytometric analyses were carried out.

show abstract

“…Several studies showed that a decreased sensitivity to FasL-induced apoptosis is based on a high LFG mRNA and protein expression rate, which was notably discovered in breast cancer cell lines. LFG downregulation therefore implicates an attractive therapeutic chance for anticancer therapy via antisense oligonucleotides or siRNA [21][22][23]. While the exact molecular mechanism of LFG regulation has not yet been fully understood, it is hypothesized as mediated by the PI3-K/Akt/LEF-1 signalling pathway because PI3-K/Akt inhibition in MCF-7 and MDA-MB-231 breast cancer cells leads to increased rates of apoptosis and reduced amounts of LFG mRNA and Protein [23,24].…”

Section: Introductionmentioning

confidence: 99%

Sensitising Breast Cancer Cells to Chemotherapy by Down Regulation of Lifeguard

Gratzke¹,

Reimers²,

Vogt³

et al. 2014

J Cancer Sci Ther

View full text Add to dashboard Cite

Introduction: Lifeguard (LFG) is an anti-apoptotic protein that inhibits programmed cell death mediated by Fas in tumour cells. The exact mechanism of action and the molecular function from LFG in the carcinogenesis of human breast cells is not clear. But the expression of LFG mRNA correlates with LEF-1 transcription factor activity. Methods:In the present study, chemotherapeutic-induced apoptotic effects were studied using MCF-7 cells as an in vitro test model. Molecular (Western blot and RT-PCR) techniques were used to investigate LFG expression. To investigate the breast cancer cell proliferation in presence of siRNA-LFG we performed fluorescent cell viability assays. Results:The results indicated that, a decrease of LFG expression using siRNA correlates with an increased sensitivity to Trastzumab and Erlotinib. Moreover, cell cycle analysis of LEF-1 siRNA-transfected human breast cancer cells revealed a significant arrest in G 2 phase. Conclusion:Taken together, our results indicate a pivotal role of LFG in the regulation of apoptosis in MCF-7 breast cancer cells.

show abstract

Silencing of anti-apoptotic transmembrane protein lifeguard sensitizes solid tumor cell lines MCF-7 and SW872 to perifosine-induced cell death activation

Cited by 8 publications

References 20 publications

Fas apoptosis inhibitory molecules: more than death‐receptor antagonists in the nervous system

Fas apoptosis inhibitory molecules: more than death‐receptor antagonists in the nervous system

TRIM21, a negative modulator of LFG in breast carcinoma MDA-MB-231 cells in vitro

Sensitising Breast Cancer Cells to Chemotherapy by Down Regulation of Lifeguard

Contact Info

Product

Resources

About