Novel Oncoprotein EPS8: A New Target for Anticancer Therapy

Li, Yuhua; Xue, Tongyuan; He, Yuanyuan; Du, Junyan

doi:10.2217/fon.13.104

Cited by 20 publications

(23 citation statements)

References 64 publications

(108 reference statements)

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“…Besides a hypoxic profile, DTC tumors also have marked expression of cancer relevant genes (Table 3) such as the metastasis-promoting tetraspanin 8 ( TSPAN8 ) [43], proliferation and migration promoting epidermal growth factor substrate 8 ( EPS8 ) [44, 45]. These results suggest that the DTC tumor phenotype could endow them with enhanced aggressiveness; indeed, it would be interesting to examine whether this phenotype might constitute a prerequisite for metastasis formation in this mouse model.…”

Section: Discussionmentioning

confidence: 99%

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

et al. 2016

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Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment.

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Section: Discussionmentioning

confidence: 99%

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

et al. 2016

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“…Eps8 is also a product of oncogene and an emerging target of anticancer therapy [79]. Eps8 is an important regulator of F-actin organization, which induces actin barbed end capping, actin bundling, and modulation of Rac GTPase-mediated actin remodeling [80,81].…”

Section: Actin Binding Proteins (Abps) That Confer Actin Filament mentioning

confidence: 99%

“…For instance, Eps8 can be tyrosine phosphorylated by a variety of protein tyrosine kinases [91]. Eps8 overexpression promotes the activity of FAK and c-Src, whereas Src can enhance tyrosine phosphorylation and protein synthesis of Eps8 which, in turn, up-regulate the expression and activity of FAK [79]. FAK has been shown to influence Arp 2/3 complex-mediated actin nucleation, modulating actin cytoskeleton organization at the basal ES of the Sertoli cell BTB through two likely mechanisms [93].…”

Section: Abps and Spermatid Transport During Spermatogenesismentioning

confidence: 99%

Actin binding proteins, spermatid transport and spermiation

Qian

Mruk

Cheng

et al. 2014

Seminars in Cell & Developmental Biology

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The transport of germ cells across the seminiferous epithelium is composed of a series of cellular events during the epithelial cycle essential to the completion of spermatogenesis. Without the timely transport of spermatids during spermiogenesis, spermatozoa that are transformed from step 19 spermatids in the rat testis fail to reach the luminal edge of the apical compartment and enter the tubule lumen at spermiation, thereby entering the epididymis for further maturation. Step 19 spermatids and/or sperms that remain in the epithelium will be removed by the Sertoli cell via phagocytosis to form phagosomes and be degraded by lysosomes, leading to subfertility and/or infertility. However, the biology of spermatid transport, in particular the final events that lead to spermiation remain elusive. Based on recent data in the field, we critically evaluate the biology of spermiation herein by focusing on the actin binding proteins (ABPs) that regulate the organization of actin microfilaments at the Sertoli-spermatid interface, which is crucial for spermatid transport during this event. The hypothesis we put forth herein also highlights some specific areas of research that can be pursued by investigators in the years to come.

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“…Animal studies HLA-A2.1/K b transgenic mice (8)(9)(10)(11)(12) week; Nanjing Biomedical Research Institute of Nanjing University, Nanjing, China) were immunized subcutaneously with 100 μg of each peptide and 100 μg pan DR epitope peptides (PADRE: AKXVAAWTLKAAA) [27] in incomplete Freund's adjuvant (Sigma) at days 1, 6, and 11. At day 12, splenocytes were collected and restimulated with each peptide as has been previously described [28].…”

Section: Enzyme-linked Immunospot (Elispot) Assaymentioning

confidence: 99%

“…The protein has subsequently been shown to be a marker of poor survival of cancer patients (reviewed in Ref. [10]). The Eps8 gene was originally identified as a substrate for the epidermal growth factor receptor (EGFR) kinase.…”

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confidence: 99%

Generation of cytotoxic T lymphocytes specific for native or modified peptides derived from the epidermal growth factor receptor pathway substrate 8 antigen

Zhou

et al. 2014

Cancer Immunol Immunother

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The ideal tumor antigen for the development of a cancer immunotherapy is one that is expressed only in tumor cells. The epidermal growth factor receptor pathway substrate 8 gene (Eps8) might be an effective antigen for cancer immunotherapy as it is overexpressed in a variety of cancer cells but not in normal tissues. In this study, the potential utility of an Eps8-derived immunotherapy was tested in vitro and in vivo. Three computer-based algorithms were used to design eight Eps8 native epitopes with potentially high binding affinity to the HLA-A2.1 molecule, which is found at a high frequency in the Chinese population. Of these eight, three peptides with a moderate affinity to the HLA-A2.1 molecule were modified at anchor residue positions to achieve stronger immunogenicity. These four modified peptides displayed stronger binding affinity to HLA-A2.1 molecules on T2 cells and a lower dissociation rate. In functional assays with human PBMCs in vitro and in HLA-A2.1/K(b) transgenic mice in vivo, CTLs primed by each native and modified peptide secreted IFN-γ and were toxic to cancer cells from a variety of tissue types in an HLA-A2.1-restricted and Eps8-specific manner. p101-109-2L and p276-284-1Y9V were superior to other modified and native epitopes both in vitro and in vivo. These results indicate that employing the native and modified epitopes identified here in Eps8-based immunotherapy for HLA-A2.1 positive cancer patients may result in efficient anticancer immune responses for diverse tumor types.

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Novel Oncoprotein EPS8: A New Target for Anticancer Therapy

Cited by 20 publications

References 64 publications

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

Actin binding proteins, spermatid transport and spermiation

Generation of cytotoxic T lymphocytes specific for native or modified peptides derived from the epidermal growth factor receptor pathway substrate 8 antigen

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