Role of Lifeguard β-isoform in the development of breast cancer

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

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“…This isoform maintains the anti‐apoptotic potential and was found to be strongly expressed in breast cancer tissues (Dastagir et al . ).…”

Section: Faim2mentioning

confidence: 97%

“…Recent studies described a new isoform of FAIM2, named FAIM2b, which lacks one of the transmembrane domains. This isoform maintains the antiapoptotic potential and was found to be strongly expressed in breast cancer tissues (Dastagir et al 2014).…”

Section: Faim2mentioning

confidence: 99%

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

Planells-Ferrer

Urresti

Coccia

et al. 2016

Journal of Neurochemistry

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“…It is possible that a part separated from the protein complex. In a study of Dastagir et al ( 15 ) in 2014 another form of LFG was examined, the β-isoform. This is a shorter form of Lifeguard and is also expressed in breast cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…This is a shorter form of Lifeguard and is also expressed in breast cancer cell lines. The study even showed that the smaller isoform of the Lifeguard enacts in an equally important role in the development of breast cancer as LFG itself ( 15 ). Hence, the band at the size of 60 kDa possibly indicates a bond between TRIM21 and β isoform of Lifeguard.…”

Section: Discussionmentioning

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

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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.

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“…Notably, primary breast cancer cell lines and tumor tissues showed a stronger expression of the isoform compared with established cell lines, in which the longer isoform was strongly expressed. The isoform of the protein may also protect cells of the mammary gland from apoptosis and result in an increase in gene expression of members of the Akt signaling pathway ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Anti-apoptotic protein Lifeguard does not act as a tumor marker in breast cancer

Maurer

Reimers

Lück³

et al. 2017

Oncology Letters

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The aim of the present study was to use an enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of Lifeguard (LFG) protein in the serum of 36 patients diagnosed with breast cancer and to compare these values with the concentrations of LFG protein in the serum of 7 healthy volunteers in order to detect a possible association between the expression of LFG in the serum and the degree of malignancy of the disease. Although there is no direct association between the LFG protein concentration in the serum and the degree of malignancy of breast cancer, a statistically significant distribution of the concentration in all investigated samples was observed. This indicated an association between the LFG protein concentration in human serum with a currently unknown factor.

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Role of Lifeguard β-isoform in the development of breast cancer

Cited by 4 publications

References 29 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

Anti-apoptotic protein Lifeguard does not act as a tumor marker in breast cancer

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