Apoptosis : an international journal on programmed cell death To sensitize cells to apoptosis, some cancers require production and response to TNF-. Over the past decade, high levels of XIAP were found to positively correlate with risk groups, worse response to chemotherapy and shorter overall and relapse-free survival [49]. BIRC6/Apollon gene expression in childhood acute leukemia: Impact on therapeutic response and prognosis. In addition, possible reasons for their modest effects, shall be presented incorporating new findings which may contribute to understanding of this phenomenon. Indeed, despite the classical assumption that childhood cancers are similar to adult ones, evidence against this model is becoming more obvious. [87], suggested that the disagreement observed between different studies could have an origin in the subcellular localization of survivin [87]. Ismail E.A.R., Mahmoud H.M., Tawfik L.M., Habashy D.M., Adly A.A.M., El-Sherif N.H., Abdelwahab M.A. Chu Q., Vincent M., Logan D., Mackay J.A., Evans W.K., Care L.C.D.S.G.o.C.C.O.s.P.i.E.-b. Cervical cancer is the most prevalent cancer in females. Increased in XIAP expression was observed in higher grades of ductal, High percentage of breast invasive ductal carcinoma with high immunoscore, Higher cytoplasmic expression is observed compared to normal tissues and, High XIAP protein related with shorter OS, Levels were higher in node positive breast cancer, cIAP1 levels did not correlate with clinicopathological features. APOPTOSIS: Aim & Scope Identification of the PANoptosome: A Molecular Platform Triggering Pyroptosis, Apoptosis, and Necroptosis (PANoptosis). (2023) Editorial: Emerging researchers in frontiers in pharmacology: obstetric and pediatric pharmacology 2022. As already stated, IAPs inhibition with Smac mimetics has demonstrated some clinical relevance, although their effectiveness has been limited when assessed as individual agents. Karasawa H., Miura K., Fujibuchi W., Ishida K., Kaneko N., Kinouchi M., Okabe M., Ando T., Murata Y., Sasaki H. Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells. the contents by NLM or the National Institutes of Health. In this regard, it should be noted that the evaluation of the Smac mimetic JP1202 on NSCLC cell line described TNF- independent pathways as being responsible for cell death induced by the treatment. Federal government websites often end in .gov or .mil. The development of compounds that mimic the action of Smac showed promise in the re-sensitization of the cell suicide defense mechanism in cancer cells, particularly in combination with other treatments. IAPs auto-ubiquitylate when Smac/DIABLO induces their RING domains E3 activity. Furthermore, other domains in IAPs are the evolutionarily conserved UBA (ubiquitin-associated) domains, which enable IAPs to bind to Lys-linked polyubiquitination [29]. To obtain Frontiers | Research progress on the mechanism of beta-cell apoptosis Also, different levels of IAPs expression in distinct patient groups have hinted at a possible involvement in treatment response and have been suggested to possess great potential as prognostic markers. Expression of inhibitor of apoptosis protein (IAP) livin/BIRC7 in acute leukemia in adults: Correlation with prognostic factors and outcome. Houghton P.J., Kang M.H., Reynolds C.P., Morton C.L., Kolb E.A., Gorlick R., Keir S.T., Carol H., Lock R., Maris J.M. Regulation of inflammasome activity. Abstract. Introduction Nuclear Factor Erythroid-2-Related Factor 2 (Nrf2) Signalling Pathway This way explain normal phenotypes in mice deficient for these proteins [20]. cIAP1 is most frequently expressed in nucleus while cIAP2 in the cytoplasm. Additionally, Grzybowska et al. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). Nuclear cIAP1 overexpression is a tumor stage-and grade-independent predictor of poor prognosis in human bladder cancer patients. The overexpression of apollon was correlated with an unfavorable prognosis in pediatric patients, a finding first observed by Sung et al. Furthermore, recent evidence demonstrating new immune-modulatory functions of IAPs, in both innate and adaptive immunity, opens new doors in terms of therapeutic opportunities. On the other hand, an interesting thing was found in triple-negative breast cancer with a specific gene signature characterized by positive expression of TNF- [111]. AIF cleavage and translocation to the cytosol is thought to be calpain-1-dependent as calpain inhibitors reduce AIF proteolysis; however, many calpain inhibitors also inhibit matrix metalloproteinase-2 (MMP-2) activity, an intracellular and extracellular protease implicated . Complex I, composed of TNFR1, TRADD, RIPK1, TRAF2 and cIAP1 is formed upon TNF- binding to TNFR. Acta Crystallogr. Themes and variations on ubiquitylation. Ultimately, a picture of multifactorial IAP overexpression and acquisition of resistance emerges. Vince J.E., Wong W.W.-L., Khan N., Feltham R., Chau D., Ahmed A.U., Benetatos C.A., Chunduru S.K., Condon S.M., McKinlay M. IAP antagonists target cIAP1 to induce TNF-dependent apoptosis. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R Evidence-Based Complementary and Alternative Medicine -. IAPs participate in the inhibition of apoptosis through several mechanisms allowing their involvement in both extrinsic and intrinsic apoptotic programs. In addition, radiation therapy appears to induce TNF- production, and, in turn, TNF- enhances radiation-mediated killing. Survivin and cyclin E2 genes expression in a cohort of Egyptian acute leukemia patients: Clinical importance and future prospects. Soon after, survivin was identified in cancer and lymphoma, Bruce/Apollon in brain cancer, livin/ML-IAP as part of a homology search and ILP-2 in testis. Evolution of the number of total citation per document and external citation per document (i.e. [142], when PD-L1 expression seemed to inhibit TNF- production in cytotoxic lymphocytes, avoiding a possible paracrine interaction with tumoral cells and the subsequent TNF-mediated cell death [142]. 5-year Impact Factor* (2021):7.915 Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. In cancer, different factors, including hypoxia or genomic instability, increase the demand for protein production, resulting in accumulation of proteins, which end up promoting ER stress [130]. Read more Data Apoptotic/necrotic death induced by Smac mimetics and TNF- crucially depends on RIPK1 because RIPK1 deficient MEFs, and cancer cells in which RIPK1 is depleted, are resistant to TNFR1 killing following treatment with Smac mimetics [46,123]. oleic acid) does not impair beta-cell function, and even inhibits the pro-apoptotic effects of saturated fatty acids ( 13 ). Chen X., Iliopoulos D., Zhang Q., Tang Q., Greenblatt M.B., Hatziapostolou M., Lim E., Tam W.L., Ni M., Chen Y. XBP1 promotes triple-negative breast cancer by controlling the HIF1 pathway. Smac, also known as DIABLO (Direct IAP Binding protein with Low pI), is a mitochondrial protein encoded in the nuclear genome. Langdon C.G., Wiedemann N., Held M.A., Mamillapalli R., Iyidogan P., Theodosakis N., Platt J.T., Levy F., Vuagniaux G., Wang S. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells. As for their anti-apoptotic activities, survivin and livin contain one BIR domain that interacts with both caspase-3 and -7, regarding the former, and with caspase-3, -7 and -9, respectively [15]. On the other hand, second mitochondrial-derived activator of caspases (Smac), the second mitochondrial-derived activator of caspases, also known as DIABLO, is a mitochondrial protein released to the cytosol upon apoptotic stimuli that antagonizes IAPs endogenously, leading to the activation of caspases and the promotion of programmed cell death in normal conditions [17]. In particular, Adamkov et al. SMAC-Mimetic BV-6 Sensitizes Therapeutic Agents-Induced Apoptosis in AML Cells. Journal Information | Oncogene - Nature However, upon substrate binding after recognition of CD40L by CD40, the ligand-receptor complex recruits TRAF3-TRAF2-cIAP for ubiquitylation of TRAF3. Gyrd-Hansen M., Darding M., Miasari M., Santoro M.M., Zender L., Xue W., Tenev T., Da Fonseca P.C., Zvelebil M., Bujnicki J.M. For safety reasons, due to the high toxicity of systemic delivery of TNF-, targeted delivery methods had to be developed. Impact Factor: 5.075 (2021); 5-Year Impact Factor: 5.305 (2021) subject Imprint Information get_app Journal Flyer . As a result, new therapies targeting IAPs expression have been designed to re-sensitize cancerous cells to apoptosis. Bianchini M., Levy E., Zucchini C., Pinski V., Macagno C., De Sanctis P., Valvassori L., Carinci P., Mordoh J. It measures the scientific influence of the average article in a journal, it expresses how central to the global scientific discussion an average article of the journal is. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. In the meantime, BIR2 can have contact with the IAP-binding motif (IBM) of the protein. In addition to apoptosis, necrosis can also be promoted by IAPs. In cancer, cells exhibiting upregulated IAPs are sometimes observed to show resistance to chemotherapy and other therapies based on the induction of apoptosis. However, there is limited information regarding the contribution of both mechanisms to actual increases in IAP expression in specific cancer types. Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which mediates staurosporine (STS) - induced cell death. IAPs: Whats in a name? Ponnelle T., Chapusot C., Martin L., Bonithon-Kopp C., Bouvier A.M., Plenchette S., Rageot D., Faivre J., Solary E., Piard F. Subcellular expression of c-IAP1 and c-IAP2 in colorectal cancers: Relationships with clinicopathological features and prognosis. The elucidation of these converging routes would signify a huge advance in prognostic evaluation, which could be incorporated in pre-treatment screening to improve targeted therapies. Rigaud S., Fondaneche M.-C., Lambert N., Pasquier B., Mateo V., Soulas P., Galicier L., Le Deist F., Rieux-Laucat F., Revy P. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Matzinger O., Viertl D., Tsoutsou P., Kadi L., Rigotti S., Zanna C., Wiedemann N., Vozenin M.-C., Vuagniaux G., Bourhis J. Collins R.J., Verschuer L.A., Harmon B.V., Prentice R.L., Pope J.H., Kerr J.F. According to Rigaud et al. Combination therapy of Smac mimetics with ICIs have provided good results in pre-clinical models. Moreover, a trial assessing its efficacy on advanced ovarian, fallopian tube and peritoneal cancer had to be canceled early due to lack of clinical benefit ({"type":"clinical-trial","attrs":{"text":"NCT01681368","term_id":"NCT01681368"}}NCT01681368). Greer R.M., Peyton M., Larsen J.E., Girard L., Xie Y., Gazdar A.F., Harran P., Wang L., Brekken R.A., Wang X. SMAC Mimetic (JP1201) Sensitizes NonSmall Cell Lung Cancers to Multiple Chemotherapy Agents in an IAP-Dependent but TNF-Independent Manner. The researchers highlighted the participation of ER stress as observed by the activation of caspase-4 [125]. Dysregulated apoptosis is often observed in other pathological conditions, such as neurodegenerative disorders (Alzheimers Disease, motor system disorders, stroke and many others) or autoimmune diseases (type I diabetes, multiple sclerosis, rheumatoid arthritis and more) [3,4]. [76] did not find mRNA or protein overexpression in malignant cells [74,76]. [72] observed higher cIAP-2 expression in stage II CRC with lymph node metastasis [72]. At the same time, NIK accumulation in NF-B alternative pathway feeds a positive loop, allowing inflammation and antitumoral effect in some cases. Yabal M., Mller N., Adler H., Knies N., Gro C.J., Damgaard R.B., Kanegane H., Ringelhan M., Kaufmann T., Heikenwlder M. XIAP restricts TNF-and RIP3-dependent cell death and inflammasome activation. Furthermore, although it is normally started as a response to ER stress to alleviate potential proteotoxicities, its pro-survival capacity can contribute to tumorigenesis and cancer progression [132,133]. For instance, it can polyubiquitylate caspase-9, when ectopically expressed in vitro [37,38,39]. Researchers assessed this compound effectiveness as a single agent in more than 100 human cancer cell lines, although only 15% of the cell lines were responsive to the treatment, MDA-MB-231 breast and SK-OV-3 ovarian cancer lines demonstrated high levels of cell death. Aryl hydrocarbon receptor is a proviral host factor and a - Science Apoptosis : an international journal on programmed cell death Therefore, further research is required to elucidate the contribution of each mechanism to both apoptosis and therapy resistance. 8600 Rockville Pike Taken together, none of them were identified as independent prognostic factors, although associations with other AML poor prognostic factors were evident [55]. APOPTOSIS -Impact factor 2022 - 2023 - Journal Impact Score CLL is a heterogeneous disease characterized by the accumulation of monoclonal mature CD5+ B cells in lymphoid organs, bone marrow and peripheral blood. Additionally, a recent clinical trial is currently recruiting participants to evaluate ASTX660s safety and efficacy in patients with refractory or relapsing T-cell lymphoma ({"type":"clinical-trial","attrs":{"text":"NCT04362007","term_id":"NCT04362007"}}NCT04362007). Furthermore, the current state of combination therapy involving Smac mimetics with traditional agents as well as with immunotherapy, will be reviewed. Apoptosis (Qualify) Latest Impact Factor IF 2021-2022 | Trend Total Number of Publications in 2020 and 2021 = 100. These pathways are associated with innate and adaptive immune responses, cell survival, proliferation, growth, or motility, depending on the cell type. On the other hand, livin negative patients presented longer survivals but only in the APL group. and JavaScript. Ma O., Cai W.-W., Zender L., Dayaram T., Shen J., Herron A.J., Lowe S.W., Man T.-K., Lau C.C., Donehower L.A. MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. These cells are known to receive support from accessory cells, such as monocyte-derived nurse-like cells, follicular dendritic cells, BMSCs or T lymphocytes, which provide pro-survival and proliferative signals. It is believed that the E3 activity of both survivins and livins RING domain might be responsible for their subcellular localization [42]. However, Smac/DIABLO is a large protein that can have significant off target effects when delivered to patients at clinical levels. Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-B activation, and is active in patient-derived xenograft models. Total Citations in 2020 and 2021 = 500. Apoptosis is a tightly regulated process in which the balance between different pro- and anti-apoptotic proteins decides the cells fate. Chai J., Du C., Wu J.-W., Kyin S., Wang X., Shi Y. Clinical significance of Smac/DIABLO expression in colorectal cancer. The Impact of Catalpol on Proliferation, Apoptosis, Migration, and - Research Article. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Despite the above, a direct link between ER stress and Smac mimetics resistance has not been established yet and, therefore, there is no information about the study of ER stress modulators and Smac mimetics combined therapy. These compounds are commonly known as Smac mimetics and have been systematically tested during the past decade. Janzen D., Tiourin E., Salehi J., Paik D., Lu J., Pellegrini M., Memarzadeh S. RETRACTED ARTICLE: An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer. However, when overexpressed, IAPs can inhibit apoptosis as observed in cancers, contributing to the acquisition of resistance to first-line treatment traditionally based on inducing DNA damage. The radiosensitizing activity of the SMAC-mimetic, Debio 1143, is TNF-mediated in head and neck squamous cell carcinoma. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Human inhibitor of apoptosis proteins: Why XIAP is the black sheep of the family. In glioblastomas, livin is correlated with worse PFS and OS rates. IAPs play a crucial role in setting a threshold for cells to undergo programmed cell death upon apoptotic stimuli. However, previous studies had not found any correlation with said features [86]. Interestingly, in vitro studies with multiple myeloma cell lines observed resistance to LCL161, while in vivo they were sensitive to it [106,107,108]. Predictive factors of damage to the Fallopian . Hiramatsu N., Messah C., Han J., LaVail M.M., Kaufman R.J., Lin J.H. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Furthermore, XIAP expression levels varied inversely with different survival indexes, such as PFS or OS, in most studies [74]. [128], XIAP protein might be involved in RIP1 and RIP3 ubiquitylation in the necrosome but, instead of promoting it, they regulate it, since deletion of XIAP renders elevated RIP1 ubiquitylation [128]. Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer. Hence, the administration of exogenous TNF- has been evaluated. INKT cells can be stimulated to produce cytokines upon Smac mimetics stimulation [146]. Media Ranking in Netherlands. Recently, some investigations have reinforced the fact that these cell death pathways (apoptosis, pyroptosis, and necroptosis) could interact with each other [21]. Front. Working Session on Improving Predictive Modeling of Mycotoxin Risk for Africa Held at the 3rd ASM2022 on 7 September 2022, in Stellenbosch, South . Nevertheless, while adaptive UPR has been shown to upregulate cIAP1, cIAP2, and XIAP through PERK (one of the sensors of the UPR), chronic ER stress was observed to downregulate XIAP protein levels, promoting a switch towards the apoptotic mechanism [134]. The ISSN (online) number for Oncogenesis is 2157-9024. As a result, abnormal expression of inhibitor apoptosis proteins (IAPs) can lead to dysregulated apoptosis promoting the development of different pathologies. XIAP inhibition and generation of reactive oxygen species enhances TRAIL sensitivity in inflammatory breast cancer cells. In the classical pathway, cIAPs have a positive regulatory function while they exhibit negative regulation in the alternative pathway. Zou H., Henzel W.J., Liu X., Lutschg A., Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome cdependent activation of caspase-3. Adamkov M., Kajo K., Vybohova D., Krajcovic J., Stuller F., Rajcani J. Correlations of survivin expression with clinicomorphological parameters and hormonal receptor status in breast ductal carcinoma. International Collaboration accounts for the articles that have been produced by researchers from several countries. Along these lines, the results obtained by Krepler et al. Likewise, models of multiple myeloma and mammary tumors obtained very high percentages for durable care rates [145]. According to Benetatos et al. Taxanes as first-line therapy for advanced non-small cell lung cancer: A systematic review and practice guideline. Gyrd-Hansen M., Meier P. IAPs: From caspase inhibitors to modulators of NF-B, inflammation and cancer. Song Z., Yao X., Wu M. Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. Xenograft models indicated similar results, where the combination therapy worked better than any of the two as single agents. However, a third study showed no correlation between the levels of XIAP protein expression and survival was found [50]. Also, CARD domains present in cIAPs appear to cooperate with c-Myc in proliferation/migration of cancers [14]. Elmore S. Apoptosis: A review of programmed cell death. Upon IAPs downregulation by antisense oligonucleotides both in vitro and in vivo, pre-clinical resistant cell models are able to engage in the apoptotic programs [36]. The P681R mutation in the spike protein, which is . Likewise, Zhu et al. GDC-0152s in vitro effectiveness was demonstrated on A2058 melanoma and different glioblastoma (GL261, U87MG, GBM6 and GBM9) cell lines, in which it successfully induced c-IAP degradation, activation of caspase-3 and -7 and apoptosis [93]. government site. A sustained activation of PI3K/NF- B pathway is critical for the survival of chronic lymphocytic leukemia B cells. Indeed, according to Yabal et al. Frontiers | Editorial: Emerging researchers in frontiers in Modulation of molecules such as tumor necrosis factor- (TNF-) present in the tumor microenvironment have been suggested to contribute to putative therapeutic efficacy of IAP inhibition, although published results do not show this consistently underlining the complex interaction between IAPs and cancer. Youssef N.S., Hewedi I.H., Abd Raboh N.M. Immunohistochemical expression of survivin in breast carcinoma: Relationship with clinicopathological parameters, proliferation and molecular classification. SJR:2.497. This is possible through the action of TRAF2 and TRAF3. [60] and later confirmed by Ismail et al. Spontaneous programmed death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro. The role of Smac mimetics in the regulation of TNF- dynamics and the promotion of apoptosis. The distinction between cytoplasmic and nuclear localization has also been made. Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa. Overall, this supports the evaluation of combination therapy in cancers, in which no therapeutic approach has provided positive results on its own. The first human IAP was described in spinal muscular atrophy (SMA), when it was found to be partially deleted or mutated in type I SMA patients. Tanaka K., Iwamoto S., Gon G., Nohara T., Iwamoto M., Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. This, again, pointed to the well-established complex nature of IAPs biology, emphasized by the fact that the inhibition of apoptosis seems to be only one of this class of proteins many functions. Apoptosis : an international journal on programmed cell death Faktor Dampak 2021-2022 | Analisis, Kecenderungan, Peringkat & Ramalan Faktor Dampak Apoptosis : an international journal on programmed cell death 2021-2022 adalah 4.677. Likewise, ER-stress-derived-NF-B activation, and consequent inflammation, have been linked to numerous cancer types. Consequently, combination approaches have been evaluated. In several cancer types IAPs are overexpressed, while their natural antagonist, the second mitochondrial-derived activator of caspases (Smac), appears to be downregulated, potentially contributing to the acquisition of resistance to traditional therapy. Furthermore, the realization that Smac mimetics may have different roles on the immune system, apart from cIAPs involvement in NF-B activation, has catalyzed different uses of these agents. Apoptosis : an international journal on programmed cell death Sect. For instance, NSCLC cell lines were sensitized to chemotherapy by the SM JP1201 even when TNF- expression was not high [125]. Accessibility [71] who found that, although the proteins were present in both nucleus and cytoplasm, cIAP-1 was most frequently expressed in the nucleus (85%) and cIAP-2 in the cytoplasm (82%) in CRC samples [71]. This phenomenon forces the remodeling of the bone marrow niche contributing to AML expansion and is potentially involved in drug resistance [129]. NAIP does not present CARD or RING domains. Additionally, studies aiming for validation of these markers show small sample sizes, have data interpretation limitations and lack standard methodologies causing reproducibility challenges [69]. This phenomenon links IAPs to immunity, although it was not the first evidence of said relationship. Along these lines, reduction of IAP levels can potentially re-sensitize cells to apoptosis. Its overexpression was also associated with advanced cancer [80]. Therefore, therapeutic approaches based on mode action of IAPs endogenous antagonist, Smac/DIABLO, have been proposed. High levels of apoptotic cells overwhelm the proper recognition and removal system of these cells. The two main signaling cascades that activate NF-B can be classified either as classical (canonical) or alternative (non-canonical) pathways. Liver cancer is a global disease with a high mortality rate and limited treatment options. Along these lines, realization that IAPs play critical roles in the modulation of said pathways opens new doors in terms of new access points to their regulation. Immediacy index*:1.731 In this regard, the multiplicity of pathways in which IAPs participate and, most importantly, their abnormal function, due to dysregulation in IAP expression, may add to the pathogenesis of diseases, such as cancer. Yang Q.-H., Du C. Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. Takeuchi H., Kim J., Fujimoto A., Umetani N., Mori T., Bilchik A., Turner R., Tran A., Kuo C., Hoon D.S. Inclusion in an NLM database does not imply endorsement of, or agreement with,