SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): Clinicopathological and prognostic significance

Harb, Ola A.; Elfeky, Mariem A.; Shafaay, Basant Sh El; Taha, Heba; Osman, Gamal; Harera, Ibtsam Shehta; Gertallah, Loay M.; AbdElmonem, Doaa Metwaly; Embaby, Ahmed

doi:10.1016/j.pathophys.2018.05.004

Cited by 31 publications

(27 citation statements)

References 32 publications

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“…When the primary panel remains inconclusive, however, parts of subsequent biomarkers (CD10, EMA, cathepsin K, c-kit, HNF1β, and E-cadherin) can be applied. We reconfirmed in the present study that E-cadherin is variably lost in CCRCC [8] and PRCC. CK7 is expressed at low levels in CCRCC, which is the most common clear-cell subtype; unusually high CK7 expression can definitely rule out the possibility of CCRCC, whereas diffuse CK7 positivity is strongly supportive of ChRCC (100%), but less certainty is reported for negative or focal staining [9].…”

Section: Discussionsupporting

confidence: 84%

Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

Kim

Joo

Lee

et al. 2020

Cancers

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In recent years, renal epithelial tumors have been among the fastest reclassifying tumors, requiring updates to the tumor classification system. Nonetheless, immunohistochemistry (IHC) remains the most widely used tool for renal epithelial tumors. In this proposal, we aimed to create the most efficient IHC panel for categorizing the diverse subtypes of renal tumors, and to find out more specific immunohistochemical results in each subtype or each antibody. A total of 214 renal tumors were analyzed using 10 possible IHC markers to differentiate subtypes, including three major renal cell carcinoma (RCC) subtypes, clear-cell type (50 cases), papillary type (50 cases), and chromophobe type (20 cases), and minor subtypes (MiT RCC, 13 cases; collecting duct carcinoma, 5 cases; and oncocytoma, 10 cases). A triple immunomarker (cytokeratin 7 (CK7)-carbonic anhydrase IX (CAIX)- alpha-methylacyl-CoA racemase (AMACR)) panel is useful in particular high-grade clear-cell tumors. If IHC remains ambiguous, the use of an adjunctive panel can be suggested, including CD10, epithelial membrane antigen, cathepsin K, c-kit, hepatocyte nuclear factor 1-β, and E-cadherin. For an efficient immunohistochemical strategy for subtyping of RCC, we conclude that the CK7-CAIX-AMACR panel is the best primary choice for screening subtyping.

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Section: Discussionsupporting

confidence: 84%

Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

Kim

Joo

Lee

et al. 2020

Cancers

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“…Previous studies have demonstrated that ZEB1 is upregulated in several types of cancer, including lung (36), gastric (37), colorectal (38) and endometrial cancers (39). Overexpression of ZEB1 has also been identified in ccRCC, and ZEB1 overexpression was significantly correlated with tumor grade, tumor, node and metastasis stage, lymph node metastasis and distant metastases (40). In addition, patients with ccRCC expressing high ZEB1 expression levels exhibited worse overall and progression-free survival when compared with low ZEB1 expression (40).…”

Section: Discussionmentioning

confidence: 97%

“…Overexpression of ZEB1 has also been identified in ccRCC, and ZEB1 overexpression was significantly correlated with tumor grade, tumor, node and metastasis stage, lymph node metastasis and distant metastases (40). In addition, patients with ccRCC expressing high ZEB1 expression levels exhibited worse overall and progression-free survival when compared with low ZEB1 expression (40). Furthermore, ZEB1 was demonstrated to be involved in several biological processes in ccRCC development and progression (41).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

Wang

et al. 2019

Exp Ther Med

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Recent studies have identified several microRNAs (miRNAs/miRs) that are dysregulated in clear cell renal cell carcinoma (ccRCC), and their dysregulation may serve important roles in the occurrence and development of ccRCC. Therefore, understanding the expression pattern and functional roles of miRNAs in ccRCC may facilitate the identification of novel therapeutic targets for the treatment of ccRCC. In the current study, reverse transcription-quantitative polymerase chain reaction was used to determine miR-508 expression levels in ccRCC tissue samples and cell lines. The cell counting kit-8 and in vitro Transwell invasion assays were used to examine the effects of miR-508 overexpression on ccRCC cell proliferation and invasion, respectively. In addition, bioinformatics analysis and dual-luciferase reporter gene assays were used to investigate the underlying mechanism of miR-508 in ccRCC cells. Furthermore, the regulatory role of miR-508 on zinc finger E-box-binding homeobox 1 (ZEB1) mRNA and protein expression in ccRCC cells was investigated using RT-qPCR and western blot analysis, respectively. Additionally, the association between miR-508 and ZEB1 expression in ccRCC tissue samples was examined. Rescue experiments were performed to determine whether the tumor suppressive effects of miR-508 may be mediated by ZEB1 in ccRCC cells. The results of the current study demonstrated that miR-508 expression was significantly downregulated in ccRCC tissue samples and cell lines. In addition, miR-508 overexpression significantly decreased the proliferation and invasion of ccRCC cells. ZEB1 was identified as a direct target gene of miR-508 in ccRCC cells and the relative expression level of ZEB1 mRNA was significantly increased in ccRCC tissue samples. Furthermore, a negative correlation between miR-508 and ZEB1 expression was identified in ccRCC tissues. ZEB1 knockdown exhibited a functional role similar to miR-508 overexpression in ccRCC cells, and restoration of ZEB1 expression significantly reversed the inhibitory effects of miR-508 on the malignant phenotype of ccRCC cells. Taken together, the results of the current study demonstrated that miR-508 may serve a tumor suppressive role in ccRCC via direct targeting of ZEB1. MiR-508 may present a novel and efficient therapeutic target for the treatment of patients with ccRCC.

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“…In contrast to the tumor-suppressive role of the SPOP protein in many human cancers described above, the oncogenic function of SPOP has been confirmed in KC. Studies have shown that SPOP is significantly upregulated in renal cell carcinoma (RCC) tissues at both the transcriptional and translational levels [43][44][45], and this upregulation was positively associated with cancer metastasis in patients with RCC [45]. In contrast, the malignant behaviors of RCC A498 and ACHN cells were reversed after SPOP knockdown using siRNA, as manifested by apoptosis induction, migration inhibition and increased sensitivity to sorafenib [116].…”

Section: Oncogenic Role Of Spop In Kidney Cancer (Kc)mentioning

confidence: 99%

The emerging role of SPOP protein in tumorigenesis and cancer therapy

Song

Pan

et al. 2020

Mol Cancer

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The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.

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SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): Clinicopathological and prognostic significance

Cited by 31 publications

References 32 publications

Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

MicroRNA‑508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion

The emerging role of SPOP protein in tumorigenesis and cancer therapy

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