RXRα acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells

Lin, Xiaofeng; Zhao, Bixing; Chen, Hang-Zhi; Ye, Xiaofeng; Yang, Chuanhui; Zhou, Haiying; Zhang, Mingqing; Lin, Sheng-Cai; Wu, Qiao

doi:10.1242/jcs.01474

Cited by 59 publications

(39 citation statements)

References 74 publications

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“…We found that cytoplasmic localization of RXRa was correlated with better prognosis in melanoma patients. This could be explained by the virtue of RXR nongenotropic pathway, which involves cytoplasmic translocalization of RXRa from the nucleus resulting in the inhibition of cell growth and induction of apoptosis in various cancer cells (21,22). Therefore, it is possible that those melanoma patients who had more cytoplasmic RXRa did also have cell growth inhibition.…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of Retinoid Receptors in Melanoma: Entailment in Tumorigenesis and Prognosis

Chakravarti¹,

Lotan²,

Diwan³

et al. 2007

Clinical Cancer Research

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Purpose: Retinoids inhibit proliferation and induce differentiation in melanoma cells. Retinoic acid receptors (RAR) and retinoid X receptors (RXR) mediate the various modulatory effects of retinoids in cells. We have studied the in situ expression of each RAR and RXR protein (a, h, g) in a large series of melanocytic lesions and correlated the expression with clinicopathologic features and prognosis of the patients. Experimental Design:Tissue microarray blocks of 226 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic and nuclear expression of RAR and RXR protein (a, h, g).Results: A significant decrease of RARh protein (P < 0.0001), nuclear expression of RARg (P < 0.0001), and RXRa (P < 0.0001) was found in primary and metastatic melanomas as compared with nevi. Loss of nuclear immunoreactivity for RARg (P = 0.048) and RXRa (P = 0.001) was observed in the lesions showing vertical growth pattern. In addition, in patients with concomitant loss of cytoplasmic staining for RARa and RXRa, the probability of overall survival (log-rank test, P = 0.002) and disease-specific survival (log-rank test, P = 0.014) was significantly lower. Conclusions: Aberrant expression of retinoid receptors seems to be a frequent event in melanoma and suggests an impairment of the retinoid pathway in this cancer. Our data indicate the loss of retinoid receptor expression with melanoma progression and suggest a possible prognostic significance of the analysis of retinoid receptors in melanoma.

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Section: Discussionmentioning

confidence: 99%

Decreased Expression of Retinoid Receptors in Melanoma: Entailment in Tumorigenesis and Prognosis

Chakravarti¹,

Lotan²,

Diwan³

et al. 2007

Clinical Cancer Research

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“…conditions the RXR-mediated targeting of Nur77/NR4A1 and of the thyroid hormone receptor to mitochondria to promote apoptosis 53,54 . Thus, in addition to a simple, on-off regulatory mechanism of RXR expression, more subtle mechanisms affecting its cellular localization control RXR transcriptional activities and may generate novel functions for this multi-faceted nuclear receptor.…”

Section: 6mentioning

confidence: 99%

Retinoid X receptors: common heterodimerization partners with distinct functions

Lefèbvre

Benomar²,

Staels

2010

Trends in Endocrinology & Metabolism

259

224

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“…Inhibition of Nur77 expression by antisense RNA prevents the apoptotic effect of AHPN/CD437. Rapid induction of Nur77 also occurs in cancer cells after stimulation of apoptosis by a variety of apoptosis-inducing agents, including calcium ionophores, etoposide (VP-16) (Li et al, 2000;Liu, 2002), and phorbol ester (Li et al, 2000;Liu, 2002;Cao et al, 2004a;Lin et al, 2004b), synthetic chenodeoxycholic acid derivatives (Jeong et al, 2003), Di-n-butyltin dichloride (Gennari et al, 2002), histone deacetylase inhibitors (Chinnaiyan et al, 2006), cadmium (Shin et al, 2004), 1,1-bis(3 0 -indolyl)-1-(p-substituted phenyl)-methanes (Chintharlapalli et al, 2005), and induced Nur77 contributes to their apoptotic effects.…”

Section: Nur77 As a Death Factormentioning

confidence: 99%

p53 and Nur77/TR3 – transcription factors that directly target mitochondria for cell death induction

2006

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The complex apoptotic functions of the p53 tumor suppressor are central to its antineoplastic activity in vivo. Conversely, p53 function is altered or attenuated in one way or another in the majority of human cancers. Besides its well-understood action as a transcriptional regulator of multiple apoptotic genes, p53 also exerts a direct pro-apoptotic role at the mitochondria by engaging in protein-protein interactions with anti-and pro-apoptotic Bcl2 family members, thereby executing the shortest known circuitry of p53 death signaling. Nur77, also known as TR3 or NGFI-B, is a unique transcription factor belonging to the orphan nuclear receptor superfamily. Even more extreme than p53, Nur77 can exert opposing biological activities of survival and death. Its activities are regulated by subcellular distribution, expression levels, protein modification and heterodimerization with retinoid X receptor. In cancer cells, Nur77 functions in the nucleus as an oncogenic survival factor, but becomes a potent killer when certain death stimuli induce its migration to mitochondria, where it binds to Bcl2 and conformationally converts it to a killer that triggers cytochrome c release and apoptosis. This review focuses on their unexpected transcription-independent pro-death programs at mitochondria and highlights the remarkable mechanistic similarities between them. Moreover, an accumulating body of evidence provides ample rationale to further investigate how these mitochondrial p53 and Nur77 pathways could become exploitable targets for new cancer therapeutics.

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RXRα acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells

Cited by 59 publications

References 74 publications

Decreased Expression of Retinoid Receptors in Melanoma: Entailment in Tumorigenesis and Prognosis

Decreased Expression of Retinoid Receptors in Melanoma: Entailment in Tumorigenesis and Prognosis

Retinoid X receptors: common heterodimerization partners with distinct functions

p53 and Nur77/TR3 – transcription factors that directly target mitochondria for cell death induction

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