Rad9 Protein Contributes to Prostate Tumor Progression by Promoting Cell Migration and Anoikis Resistance

Broustas, Constantinos G.; Zhu, Aiping; Lieberman, Howard B.

doi:10.1074/jbc.m112.402784

Cited by 36 publications

(53 citation statements)

References 40 publications

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“…With the advantages of specificity and high efficiency, the siRNA technique has become a common reverse genetics method of gene function research both in vivo and in vitro [29]. Suppression of endogenous Annexin A3 in BGC823 cells using siRNA, inhibited gastric cancer cell proliferation, promoted the expression of cell cycle negative regulators, p21 and p27, and suppressed the expression of cyclin D1, which enhances cell proliferation by promoting cell cycle progression from G1-S [32,34]. We also found that expression of the cellular proliferation marker, PCNA, decreased after Annexin A3-siRNA treatment.…”

Section: Discussionmentioning

confidence: 99%

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Impact of Annexin A3 expression in gastric cancer cells

Yu¹,

Y²,

Fan³

et al. 2014

neo

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Annexin A3 participates in various biological processes, including tumorigenesis, drug resistance, and metastasis. The aim of this study was to investigate the expression of Annexin A3 in gastric cancer and its relationship with cell differentiation, migration, and invasion of gastric cancer cells. Annexin A3 expression in gastric cancer tissues was detected by quantitative real-time PCR and Western blotting. The proliferation of gastric cancer cells was measured by the MTT assay. Cell migration and invasion were determined via wound healing and transwell assays, respectively. Knock down of endogenous Annexin A3 in gastric cancer BGC823 cells was performed using siRNA technology. The expression of Annexin A3 was significantly upregulated in gastric cancer tissues, and negatively correlated with the differentiation degree. Silencing of endogenous Annexin A3 suppressed the proliferation, migration, and invasion of BGC823 cells. Additionally, the expression of p21, p27, TIMP-1, and TIMP-2 was upregulated, and the expression of PCNA, cyclin D1, MMP-1, and MMP-2 decreased in cells treated with Annexin A3-siRNA. Annexin A3 was upregulated in gastric cancer cells. Deletion of endogenous Annexin A3 significantly inhibited gastric cancer cell proliferation, migration, and invasion.

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Section: Discussionmentioning

confidence: 99%

“…Enhancement of invasion/migration abilities provides the basis for tumor metastasis, which is the result of malignant tumor progression [34]. Previous studies have reported that Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo [35].…”

Section: Discussionmentioning

confidence: 99%

Impact of Annexin A3 expression in gastric cancer cells

Yu¹,

Y²,

Fan³

et al. 2014

neo

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“…Further, RAD9 functions in tumor metastasis, and thus its activity is not limited to initial tumor formation. Down regulation of RAD9 in prostate cancer cells in culture impairs metastasis-related phenotypes, including migration, invasion, and anchorage-independent growth, as well as sensitizes those cells to anoikis (41,42), which is programmed death induced when cells are not attached to a matrix (43). Typically, metastatic cells are anoikis resistant, enabling them to remain viable as they travel through the bloodstream for eventual localization in distal sites.…”

Section: Rad9 and Prostate Cancermentioning

confidence: 99%

“…Typically, metastatic cells are anoikis resistant, enabling them to remain viable as they travel through the bloodstream for eventual localization in distal sites. RAD9 affects cell migration and invasion by modulating integrin β1 protein level, and anoikis resistance by modulating AKT kinase activation (42). …”

Section: Rad9 and Prostate Cancermentioning

confidence: 99%

Prostate cancer: unmet clinical needs and RAD9 as a candidate biomarker for patient management

et al. 2018

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Prostate cancer is a complex disease, with multiple subtypes and clinical presentations. Much progress has been made in recent years to understand the underlying genetic basis that drives prostate cancer. Such mechanistic information is useful for development of novel therapeutic targets, to identify biomarkers for early detection or to distinguish between aggressive and indolent disease, and to predict treatment outcome. Multiple tests have become available in recent years to address these clinical needs for prostate cancer. We describe several of these assays, summarizing test details, performance characteristics, and acknowledging their limitations. There is a pressing unmet need for novel biomarkers that can demonstrate improvement in these areas. We introduce one such candidate biomarker, RAD9, describe its functions in the DNA damage response, and detail why it can potentially fill this void. RAD9 has multiple roles in prostate carcinogenesis, making it potentially useful as a clinical tool for men with prostate cancer. RAD9 was originally identified as a radioresistance gene, and subsequent investigations revealed several key functions in the response of cells to DNA damage, including involvement in cell cycle checkpoint control, at least five DNA repair pathways, and apoptosis. Further studies indicated aberrant overexpression in approximately 45% of prostate tumors, with a strong correlation between RAD9 abundance and cancer stage. A causal relationship between RAD9 and prostate cancer was first demonstrated using a mouse model, where tumorigenicity of human prostate cancer cells after subcutaneous injection into nude mice was diminished when RNA interference was used to reduce the normally high levels of the protein. In addition to activity needed for the initial development of tumors, cell culture studies indicated roles for RAD9 in promoting prostate cancer progression by controlling cell migration and invasion through regulation of ITGB1 protein levels, and anoikis resistance by modulating AKT activation. Furthermore, RAD9 enhances the resistance of human prostate cancer cells to radiation in part by regulating ITGB1 protein abundance. RAD9 binds androgen receptor and inhibits androgen-induced androgen receptor's activity as a transcription factor. Moreover, RAD9 also acts as a gene-specific transcription factor, through binding p53 consensus sequences at target gene promoters, and this likely contributes to its oncogenic activity. Given these diverse and extensive activities, RAD9 plays important roles in the initiation and progression of prostate cancer and can potentially serve as a valuable biomarker useful in the management of patients with this disease.

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“…For example, anoikis promotes the luminal clearance during mammary gland development, which to some extent explains the formation of our inner organ (Debnath, 2008). Moreover, a bulk of evidences has proved that anoikis resistance is intimately involved in the tumorigenesis and metastasis of various cancers, such as lung, colon, and prostate cancers (Horbinski et al, 2010;Broustas et al, 2012;Taddei et al, 2012;Vigil et al, 2012;Zheng et al, 2012). Therefore, the studies and summarizations of the regulatory mechanism(s) of anoikis are fundamental to the intervention of tumor metastasis.…”

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confidence: 99%

Integration of Autophagy and Anoikis Resistance in Solid Tumors

Yang¹,

Zheng

Yan³

et al. 2013

The Anatomical Record

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Macroautophagy or autophagy is a lysosome-dependent process in which enzymatic degradation and recycling of cytosolic components occurred due to stressful conditions. This cellular arrangement imparts anoikis resistance in solid tumors. Anoikis, a special form of apoptosis occurring when cells detach from the extracellular matrix, is a critical mechanism in maintaining tissue homeostasis and development. Anoikis resistance facilitates tumorigenesis and metastasis. However, the complexity of the role of autophagy in tumor is underscored by evidence that autophagy can function as both a pro-survival or pro-death depending on the context and the stimuli, which are likely exploitable for tumor therapy. This review focuses on recent progress in understanding anoikis resistance and autophagy signaling, paying particular attention to its relevance in solid tumor metastasis. Anat Rec, 296:1501Rec, 296: -1508

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Rad9 Protein Contributes to Prostate Tumor Progression by Promoting Cell Migration and Anoikis Resistance

Cited by 36 publications

References 40 publications

Impact of Annexin A3 expression in gastric cancer cells

Impact of Annexin A3 expression in gastric cancer cells

Prostate cancer: unmet clinical needs and RAD9 as a candidate biomarker for patient management

Integration of Autophagy and Anoikis Resistance in Solid Tumors

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