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Search Results: 1 - 10 of 71380 matches for " Shi-Yong Sun "
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Understanding the Role of the Death Receptor 5/FADD/caspase-8 Death Signaling in Cancer Metastasis
Shi-Yong Sun
Molecular and Cellular Pharmacology , 2011,
Abstract: The normal function of the extrinsic apoptotic pathway is to mediate apoptosis. Thus, this pathway is generally recognized to be critical in host immune surveillance against cancer. However, many studies have suggested that some key components in this pathway including Fas, death receptor 5 (DR5), Fas-associated death domain (FADD) and caspase-8 may contribute to cancer growth or metastasis. Our recent study on DR5 and caspase-8 expression in human head and neck cancer tissues indicate that high caspase-8 either alone or along with high DR5 in tumor tissue from patients with lymph node metastasis is significantly associated with poor disease-free survival and overall survival, suggesting that these proteins may be involved in positive regulation of cancer metastasis. Thus, efforts should be made to better understand the role of the death receptor 5/FADD/caspase-8 death signaling in regulation of cancer metastasis.
Impact of genetic alterations on mTOR-targeted cancer therapy
Shi-Yong Sun
Chinese Journal of Cancer , 2013, DOI: 10.5732/cjc.013.10005
Abstract: Rapamycin and its derivatives (rapalogs), a group of allosteric inhibitors of mammalian target of rapamycin (mTOR), have been actively tested in a variety of cancer clinical trials, and some have been approved by the Food and Drug Administration for the treatment of certain types of cancers. However, the single agent activity of these compounds in many tumor types remains modest. The mTOR axis is regulated by multiple upstream signaling pathways. Because the genes (e.g., PIK3CA, KRAS, PTEN, and LKB1) that encode key components in these signaling pathways are frequently mutated in human cancers, a subset of cancer types may be addicted to a given mutation, leading to hyperactivation of the mTOR axis. Thus, efforts have been made to demonstrate the potential impact of genetic alterations on rapalog-based or mTOR-targeted cancer therapy. This review will primarily summarize research advances in this direction.
PPAR and Apoptosis in Cancer
Heath A. Elrod,Shi-Yong Sun
PPAR Research , 2008, DOI: 10.1155/2008/704165
Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand binding transcription factors which function in many physiological roles including lipid metabolism, cell growth, differentiation, and apoptosis. PPARs and their ligands have been shown to play a role in cancer. In particular, PPAR ligands including endogenous prostaglandins and the synthetic thiazolidinediones (TZDs) can induce apoptosis of cancer cells with antitumor activity. Thus, PPAR ligands have a potential in both chemoprevention and therapy of several types of cancer either as single agents or in combination with other antitumor agents. Accordingly, the involvement of PPAR and its ligands in regulation of apoptosis of cancer cells have been extensively studied. Depending on cell types or ligands, induction of apoptosis in cancer cells by PPAR ligands can be either PPAR-dependent or -independent. Through increasing our understanding of the mechanisms of PPAR ligand-induced apoptosis, we can develop better strategies which may include combining other antitumor agents for PPAR-targeted cancer chemoprevention and therapy. This review will highlight recent research advances on PPAR and apoptosis in cancer.
Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma
Zhigang Kang,Shi-Yong Sun,Liang Cao
ISRN Oncology , 2012, DOI: 10.5402/2012/395952
Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma
Zhigang Kang,Shi-Yong Sun,Liang Cao
ISRN Oncology , 2012, DOI: 10.5402/2012/395952
Abstract: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. It is believed to arise from skeletal muscle progenitors, preserving the expression of genes critical for embryonic myogenic development such as MYOD1 and myogenin. RMS is classified as embryonal, which is more common in younger children, or alveolar, which is more prevalent in elder children and adults. Despite aggressive management including surgery, radiation, and chemotherapy, the outcome for children with metastatic RMS is dismal, and the prognosis has remained unchanged for decades. Apoptosis is a highly regulated process critical for embryonic development and tissue and organ homeostasis. Like other types of cancers, RMS develops by evading intrinsic apoptosis via mutations in the p53 tumor suppressor gene. However, the ability to induce apoptosis via the death receptor-dependent extrinsic pathway remains largely intact in tumors with p53 mutations. This paper focuses on activating extrinsic apoptosis as a therapeutic strategy for RMS by targeting the death receptor DR5 with a recombinant TRAIL ligand or agonistic antibodies directed against DR5. 1. Introduction Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue tumor. Despite extensive research and aggressive clinical management, the overall outcome for children with metastatic disease is dismal with a prognosis largely unchanged in decades [1, 2]. RMS tumors are histologically classified into two major subtypes, embryonic (ERMS) and alveolar (ARMS), which are associated with unique genetic changes. The majority of ARMSs are characterized by the presence of PAX3/7:FOXO1 translocation [3, 4]. ERMSs, on the other hand, are more frequently associated with activated RAS signaling via mutations in RAS genes or deletions in NF1, a tumor suppressor that encodes an RAS inhibitor [5–7]. The two subtypes of RMS also have distinct prognoses. ERMSs are often found in younger patients who generally do better, whereas ARMSs are more frequently diagnosed in adolescents and young adults who have a worse prognosis with a five-year survival rate of less than 50% [8–11]. Additional mutations in tumor suppressors are important for the development of RMS. In particular, RMS is the most common pediatric cancer in families with Li-Fraumeni syndrome [12]. Mutations in p53 are important for pathogenesis and commonly found in RMS [13, 14]. Despite advances in radiation and chemotherapy, there has been little change in the 5-year survival rate for pediatric RMS [10]. The cure rate for advanced RMS is not expected to improve
Mono- or Double-Site Phosphorylation Distinctly Regulates the Proapoptotic Function of Bax
Qinhong Wang,Shi-Yong Sun,Fadlo Khuri,Walter J. Curran,Xingming Deng
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013393
Abstract: Bax is the major multidomain proapoptotic molecule that is required for apoptosis. It has been reported that phosphorylation of Bax at serine(S) 163 or S184 activates or inactivates its proapoptotic function, respectively. To uncover the mechanism(s) by which phosphorylation regulates the proapoptotic function of Bax, a series of serine (S)→ alanine/glutamate (A/E) Bax mutants, including S163A, S184A, S163E, S184E, S163E/S184A (EA), S163A/S184E (AE), S163A/S184A (AA) and S163E/S184E (EE), were created to abrogate or mimic, respectively, either single or double-site phosphorylation. The compound Bax mutants (i.e. EA and AE) can flesh out the functional contribution of individual phosphorylation site(s). WT and each of these Bax mutants were overexpressed in Bax?/? MEF or lung cancer H157 cells and the proapoptotic activities were compared. Intriguingly, expression of any of Bax mutants containing the mutation S→A at S184 (i.e. S184A, EA or AA) represents more potent proapoptotic activity as compared to WT Bax in association with increased 6A7 epitope conformational change, mitochondrial localization/insertion and prolonged half-life. In contrast, all Bax mutants containing the mutation S→E at S184 (i.e. S184E, AE or EE) have a mobility-shift and fail to insert into mitochondrial membranes with decreased protein stability and less apoptotic activity. Unexpectedly, mutation either S→A or S→E at S163 site does not significantly affect the proapoptotic activity of Bax. These findings indicate that S184 but not S163 is the major phosphorylation site for functional regulation of Bax's activity. Therefore, manipulation of the phosphorylation status of Bax at S184 may represent a novel strategy for cancer treatment.
Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of Geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis
Shuzhen Chen, Lei Fu, Shruti M Raja, Ping Yue, Fadlo R Khuri, Shi-Yong Sun
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-23
Abstract: The GGTase I inhibitor GGTI-298 induced apoptosis and augmented tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. GGTI-298 induced DR4 and DR5 expression and reduced c-FLIP levels. Enforced c-FLIP expression or DR5 knockdown attenuated apoptosis induced by GGTI-298 and TRAIL combination. Surprisingly, DR4 knockdown sensitized cancer cells to GGTI298/TRAIL-induced apoptosis. The combination of GGTI-298 and TRAIL was more effective than each single agent in decreasing the levels of IκBα and p-Akt, implying that GGTI298/TRAIL activates NF-κB and inhibits Akt. Interestingly, knockdown of DR5, but not DR4, prevented GGTI298/TRAIL-induced IκBα and p-Akt reduction, suggesting that DR5 mediates reduction of IκBα and p-Akt induced by GGTI298/TRAIL. In contrast, DR4 knockdown further facilitated GGTI298/TRAIL-induced p-Akt reduction.Both DR5 induction and c-FLIP downregulation contribute to GGTI-298-mediated augmentation of TRAIL-induced apoptosis. Moreover, DR4 appears to play an opposite role to DR5 in regulation of GGTI/TRAIL-induced apoptotic signaling.There are two major apoptotic signaling pathways: the intrinsic mitochondria-mediated pathway and the extrinsic death receptor-induced pathway, and these pathways are linked by the truncated proapoptotic protein Bid [1]. The extrinsic apoptotic pathway is negatively regulated primarily by the cellular FLICE-inhibitory protein (c-FLIP), including both long (FLIPL) and short (FLIPS) forms, through inhibition of caspase-8 activation, whereas the intrinsic apoptotic pathway is negatively regulated by multiple proteins including survivin [2]. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to its receptors: death receptor 4 (DR4, also named TRAIL-R1) and death receptor 5 (DR5, also named TRAIL-R2) to activate the extrinsic apoptotic pathway [3]. Recently TRAIL has received much attention because it preferentially induces apoptosis in transforme
Shi-Yong Liu,Shan-Shan Sun,Ting-Ting Zheng,Xiang-Lei Zheng
Acta Crystallographica Section E , 2011, DOI: 10.1107/s1600536811010361
Abstract: In the title compound, C19H16N2O2, the benzene ring and naphthyl ring system are inclined at a dihedral angle of 16.1 (3)°. An intramolecular O—H...N hydrogen bond influences the molecular conformation. In the crystal, molecules are linked through N—H...O hydrogen bonds into chains running along the a axis.
Shi-Yong Liu,Shan-Shan Sun,Ting-Ting Zheng,Xiang-Lei Zheng
Acta Crystallographica Section E , 2011, DOI: 10.1107/s160053681101035x
Abstract: In the title compound, C19H16N2O2, the benzene ring and the naphthyl ring system form a dihedral angle of 8.7 (3)° and an intramolecular O—H...N hydrogen bond generates an S(6) ring. In the crystal, molecules are linked by N—H...O hydrogen bonds, forming C(4) chains propagating in [001].
(E)-N′-(2-Hydroxy-3,5-diiodobenzylidene)nicotinohydrazide acetonitrile monosolvate
Shan-Shan Sun,Shi-Yong Liu,Ting-Ting Zheng,Xiao-Ling Wang
Acta Crystallographica Section E , 2011, DOI: 10.1107/s1600536811020770
Abstract: In the hydrazone molecule of the title compound, C13H9I2N3O2·CH3CN, the aromatic rings form a dihedral angle of 9.4 (3)°. In the crystal structure, intermolecular I...N interactions [3.099 (4) ] link hydrogen-bonded aggregates of the hydrozone and solvent molecules related by translation along the b axis into chains. An intramolecular O—H...N hydrogen bond forms an S(6) ring.
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