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Entity | Various carcinomas and melanoma |
Note | RPS27 overexpression has been reported in many cancers including prostate cancer (Fernandez-Pol et al., 1997), colorectal cancer (Ganger et al., 1997), liver cancer (Ganger et al., 2001), breast cancer (Atsuta et al., 2002), head and neck squamous cell cancer (HNSCC) (Stack et al., 1999; Stack et al., 2004; Lee et al., 2004), gastric cancer (Wang, et al., 2006), as well as, melanoma (Santa Cruz et al., 1997). Since high serum levels of RPS27 have been found in cancer patients, especially in head and neck squamous cell carcinoma (HNSCC), the protein can be used as a tumor marker (Fernandez-Pol et al., 1996; Lee et al., 2004; Stack et al. 2004). |
Prognosis | It was reported that RPS27 levels correlate with tumor stage in patients with gastric cancer, thus high levels serve as a poor prognostic indicator (Wang et al., 2006). |
Oncogenesis | The mechanism behind RPS27 overexpression is currently under investigation. One explanation recently offered arises from the relationship between RPS27, MDM2 and p53: RPS27 is a p53 repressible protein (He and Sun, 2007; Li et al., 2007). A 2011 study found that it competes with p53 for a central acidic binding domain on MDM2. Once bound, MDM2 is stimulated to ubiquinate and degrade the RPS27 or p53, whichever it is bound to. When RPS27 levels are elevated, it can out-compete p53 for MDM2 binding and subsequent degradation, thus stabilizing p53 levels. This would be an appropriate cellular response to genotoxic stress. The same study also found that mutant p53 cannot suppress RPS27, only the wild-type can. Since mutated p53 is found in almost 50% of all human cancers, RPS27 overexpression logically follows. Furthermore, stabilization of mutant p53 levels associated with RPS27 abundance could provide malignant cells with a growth advantage (Xiong et al., 2011). RPS27 knockdown was found to enhance spontaneous apoptosis of tumor cells via caspase-3 activation (Wang et al., 2006; Yang et al., 2011). HNSCC: some have questioned if RPS27 overexpression is the cause or result of cancer. A 2010 study overexpressed RPS27 in a line of HNSCC cells to study the impact on tumor behavior. They found that RPS27 overexpression resulted in reduced cancer cell growth, proliferation rate and angiogenesis. RPS27 overexpression was also found to reduce the mRNA of Paxillin, a focal adhesion protein up regulated in HNSCC and many other cancer cells. RPS27 induced Paxillin repression offers a possible explanation for the decreased HNSCC growth (Dai et al., 2010). |
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Identification of metallopanstimulin-1 as a member of a tumor associated antigen in patients with breast cancer. |
Atsuta Y, Aoki N, Sato K, Oikawa K, Nochi H, Miyokawa N, Hirata S, Kimura S, Sasajima T, Katagiri M. |
Cancer Lett. 2002 Aug 8;182(1):101-7. |
PMID 12175529 |
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Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes. |
Balasubramanian S, Zheng D, Liu YJ, Fang G, Frankish A, Carriero N, Robilotto R, Cayting P, Gerstein M. |
Genome Biol. 2009;10(1):R2. Epub 2009 Jan 5. |
PMID 19123937 |
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Extraribosomal function of metallopanstimulin-1: reducing paxillin in head and neck squamous cell carcinoma and inhibiting tumor growth. |
Dai Y, Pierson SE, Dudney WC, Stack BC Jr. |
Int J Cancer. 2010 Feb 1;126(3):611-9. |
PMID 19642098 |
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Expression of metallopanstimulin and oncogenesis in human prostatic carcinoma. |
Fernandez-Pol JA, Fletcher JW, Hamilton PD, Klos DJ. |
Anticancer Res. 1997 May-Jun;17(3A):1519-30. |
PMID 9179190 |
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Differential expression of metallopanstimulin/S27 ribosomal protein in hepatic regeneration and neoplasia. |
Ganger DR, Hamilton PD, Klos DJ, Jakate S, McChesney L, Fernandez-Pol JA. |
Cancer Detect Prev. 2001;25(3):231-6. |
PMID 11425264 |
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MDMX regulation of p53 response to ribosomal stress. |
Gilkes DM, Chen L, Chen J. |
EMBO J. 2006 Nov 29;25(23):5614-25. Epub 2006 Nov 16. |
PMID 17110929 |
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Ribosomal protein S27L is a direct p53 target that regulates apoptosis. |
He H, Sun Y. |
Oncogene. 2007 Apr 26;26(19):2707-16. Epub 2006 Oct 23. |
PMID 17057733 |
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A new assay to screen for head and neck squamous cell carcinoma using the tumor marker metallopanstimulin. |
Lee WJ, Keefer K, Hollenbeak CS, Stack BC Jr. |
Otolaryngol Head Neck Surg. 2004 Oct;131(4):466-71. |
PMID 15467619 |
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Ribosomal protein S27-like, a p53-inducible modulator of cell fate in response to genotoxic stress. |
Li J, Tan J, Zhuang L, Banerjee B, Yang X, Chau JF, Lee PL, Hande MP, Li B, Yu Q. |
Cancer Res. 2007 Dec 1;67(23):11317-26. |
PMID 18056458 |
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Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin. |
Santa Cruz DJ, Hamilton PD, Klos DJ, Fernandez-Pol JA. |
J Cutan Pathol. 1997 Oct;24(9):533-42. (REVIEW) |
PMID 9404850 |
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Metallopanstimulin as a marker for head and neck cancer. |
Stack BC Jr, Hollenbeak CS, Lee CM, Dunphy FR, Lowe VJ, Hamilton PD. |
World J Surg Oncol. 2004 Dec 14;2:45. |
PMID 15598348 |
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In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity. |
Wang YW, Qu Y, Li JF, Chen XH, Liu BY, Gu QL, Zhu ZG. |
Clin Cancer Res. 2006 Aug 15;12(16):4965-73. |
PMID 16914586 |
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Ribosomal protein S27-like and S27 interplay with p53-MDM2 axis as a target, a substrate and a regulator. |
Xiong X, Zhao Y, He H, Sun Y. |
Oncogene. 2011 Apr 14;30(15):1798-811. Epub 2010 Dec 20. |
PMID 21170087 |
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Knockdown of metallopanstimulin-1 inhibits NF-?B signaling at different levels: The role of apoptosis induction of gastric cancer cells. |
Yang ZY, Qu Y, Zhang Q, Wei M, Liu CX, Chen XH, Yan M, Zhu ZG, Liu BY, Chen GQ, Wu YL, Gu QL. |
Int J Cancer. 2011 Jul 27. doi: 10.1002/ijc.26331. [Epub ahead of print] |
PMID 21796632 |
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