Expression and Cytoplasmic Localization of SAM68 Is a Significant and Independent Prognostic Marker for Renal Cell Carcinoma

Zhang, Zhiling; Li, Jun; Zheng, Huiru; Yu, Chunping; Chen, Jin; Liu, Zhuowei; Li, Manzhi; Zeng, Musheng; Zhou, Fangjian; Song, Li

doi:10.1158/1055-9965.epi-09-0097

Cited by 52 publications

(64 citation statements)

References 44 publications

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“…Increased expression of Sam68 correlated with poor prognosis also in patients affected by renal carcinoma (Zhang et al 2009). Notably, in advanced stages of both breast (Song et al 2010) and renal (Zhang et al 2009) tumors, Sam68 was localized also in the cytoplasm.…”

Section: Role Of Sam68 In Cancermentioning

confidence: 87%

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The RNA-binding protein Sam68 is a multifunctional player in human cancer

Bielli

Busà

Paronetto

et al. 2011

Endocrine-Related Cancer

148

145

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Src associated in mitosis, of 68 kDa (Sam68) is a KH domain RNA-binding protein that belongs to the signal transduction and activation of RNA family. Although ubiquitously expressed, Sam68 plays very specialized roles in different cellular environments. In most cells, Sam68 resides in the nucleus and is involved in several steps of mRNA processing, from transcription, to alternative splicing, to nuclear export. In addition, Sam68 translocates to the cytoplasm upon cell stimulation, cell cycle transitions or viral infections, where it takes part to signaling complexes and associates with the mRNA translation machinery. Recent evidence has linked Sam68 function to the onset and progression of endocrine tumors, such as prostate and breast carcinomas. Notably, all the biochemical activities reported for Sam68 seem to be implicated in carcinogenesis. Herein, we review the recent advancement in the knowledge of Sam68 function and regulation and discuss it in the frame of its participation to neoplastic transformation and tumor progression.

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Section: Role Of Sam68 In Cancermentioning

confidence: 87%

“…Notably, in advanced stages of both breast (Song et al 2010) and renal (Zhang et al 2009) tumors, Sam68 was localized also in the cytoplasm. In both cases, cytoplasmic localization of the protein represented an independent factor of poor prognosis.…”

Section: Role Of Sam68 In Cancermentioning

confidence: 99%

The RNA-binding protein Sam68 is a multifunctional player in human cancer

Bielli

Busà

Paronetto

et al. 2011

Endocrine-Related Cancer

148

145

View full text Add to dashboard Cite

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“…Previous studies revealed that the PI3K/AKT signal transduction cascade was required for cell-cycle progression through the G 1 -phase (25). In addition, activation of PI3K/AKT decreases the cellular levels of p21Cip1 and p27Kip1, and induces cyclin D1 expression, thereby promoting cell proliferation (14,26). The modulation of these cell-cycle regulators by PI3K/AKT is accomplished either directly or indirectly through inhibiting the phosphorylation and activation of FOXO3a (14,27,28).…”

Section: Discussionmentioning

confidence: 99%

“…PHLPP1 and PHLPP2 belong to a novel family of Ser/Thr protein phosphatases and play central roles in maintaining cell survival suppression through negatively regulating the signaling pathways activated by AKT, PKC, MAPK, and Mst1 (29)(30)(31)(32). Evidence has recently emerged to suggest that PHLPP1 and PHLPP2 act as tumor suppressor genes, and their expression is frequently depleted in a variety of human cancers, including breast cancer, prostate cancer, and colorectal cancer (26,33). As Ser/Thr protein phosphatases, PHLPP1 and PHLPP2 can directly dephosphorylate AKT to inhibit AKT signaling activity, which promotes apoptosis (15,30,33).…”

Section: Discussionmentioning

confidence: 99%

“…As Ser/Thr protein phosphatases, PHLPP1 and PHLPP2 can directly dephosphorylate AKT to inhibit AKT signaling activity, which promotes apoptosis (15,30,33). Overexpression of PHLPP1 and PHLPP2 in cancer cell lines decreases cell proliferation and tumorigenesis both in vitro and in xenograft models (26,30,(33)(34)(35)(36)(37). In colorectal cancer cells, stable overexpression of PHLPP1 or PHLPP2 blocked the G 2 -M transition or induced G 1 cell-cycle arrest, thus decreasing the rate of cell proliferation (26).…”

Section: Discussionmentioning

confidence: 99%

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microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2

Liao

Wang

et al. 2013

Clinical Cancer Research

110

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Purpose: To investigate the clinicopathologic significance, role, and mechanism of action of microRNA-224 (miR-224) in colorectal cancer.Experimental Design: Real-time PCR was used to quantify miR-224 expression. The association of miR-224 with the clinicopathologic features and survival was evaluated in 110 colorectal cancer patients. The role of miR-224 in colorectal cancer was investigated using in vitro and in vivo assays. Luciferase reporter assays were conducted to confirm target gene associations.Results: miR-224 was overexpressed in colorectal cancer. High-level expression of miR-224 was significantly associated with an aggressive phenotype and poor prognosis. Overexpression of miR-224 promoted colorectal cancer cell proliferation in vitro and tumor growth in vivo. Specifically, miR-224 accelerated the G 1 -S phase transition through activation of AKT/FOXO3a signaling, downregulation of p21Cip1 and p27Kip1, and upregulation of cyclin D1. Moreover, both PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, antagonists of PI3K/AKT signaling, were confirmed as bona fide targets of miR-224. miR-224 directly targeted the 3 0 -untranslated regions of the PHLPP1 and PHLPP2 mRNAs and repressed their expression. Conclusion: This study reveals functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHLPP2 in the pathogenesis of colorectal cancer. miR-224 not only plays important roles in the regulation of cell proliferation and tumor growth in colorectal cancer, but also has potential as a prognostic marker or therapeutic target for colorectal cancer.

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Sam68 is required for the growth and survival of nonmelanoma skin cancer

Sun

Xia

et al. 2019

Cancer Medicine

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Although targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of nonmelanoma skin cancer (NMSC), the most common type of skin cancer, remains obscure. Here, we report that Src‐associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2‐transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2‐transgenic mice. Moreover, Sam68 plays a critical role in DNA damage‐induced DNA repair and nuclear factor kappa B (NF‐κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together, our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC.

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Expression and Cytoplasmic Localization of SAM68 Is a Significant and Independent Prognostic Marker for Renal Cell Carcinoma

Cited by 52 publications

References 44 publications

The RNA-binding protein Sam68 is a multifunctional player in human cancer

The RNA-binding protein Sam68 is a multifunctional player in human cancer

microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2

Sam68 is required for the growth and survival of nonmelanoma skin cancer

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