Increased expression of caveolin‐1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma

Joo, Hee Jae; Oh, Dong Keun; Kim, Y.S.; Lee, K.B.; Kim, S.J.

doi:10.1111/j.1464-410x.2004.04604.x

Cited by 138 publications

(115 citation statements)

References 29 publications

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“…Support for this notion is in part provided by other clinical studies that show that the overexpression of caveolin-1 is correlated with increased microvessel density within tumours not only of the kidney (Joo et al, 2004) but also the prostate (Yang et al, 2007). Therefore, we present a hypothetical model (adapted from Li et al, 2003) for the coordinated role of caveolin-1 and the AKT/mTOR pathway in RCC disease progression.…”

Section: Discussionmentioning

confidence: 92%

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Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

et al. 2008

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We previously reported that tumour-associated caveolin-1 is a potential biomarker in renal cell carcinoma (RCC), whose overexpression predicts metastasis following surgical resection for clinically confined disease. Much attention has recently focused on the AKT/mTOR pathway in a number of malignancies, including RCC. Since caveolin-1 and the AKT/mTOR signalling cascade are independently shown to be important regulators of tumour angiogenesis, we hypothesised that caveolin-1 interacts with the AKT/ mTOR pathway to drive disease progression and metastasis in RCC. The aims of this study were to determine (i) the expression status of the activated AKT/mTOR pathway components (phosphorylated forms) in RCC and (ii) their prognostic value when combined with caveolin-1. Immunohistochemistry for caveolin-1, pAKT, pmTOR, pS6 and p4E-BP1 was performed on tissue microarrays from 174 clinically confined RCCs. Significantly decreased mean disease-free survival was observed when caveolin-1 was coexpressed with either pAKT (2.95 vs 6.14 years), pmTOR (3.17 vs 6.28 years), pS6 (1.45 vs 6.62 years) or p4E-BP1 (2.07 vs 6.09 years) than when neither or any one single biomarker was expressed alone. On multivariate analysis, the covariate of 'caveolin-1/AKT' (neither alone were influential covariates) was a significant influential indicator of poor disease-free survival with a hazard ratio of 2.13 (95% CI: 1.15 -3.92), higher than that for vascular invasion. Tumours that coexpressed caveolin-1 and activated mTOR components were more likely to be larger, higher grade and to show vascular invasion. Our results provide the first clinical evidence that caveolin-1 cooperates with an activated AKT/mTOR pathway in cancer and may play an important role in disease progression. We conclude that evaluation of the 'caveolin-1/AKT/mTOR axis' in primary kidney tumours will identify subsets of RCC patients who require greater postoperative surveillance and more intensive treatment.

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Section: Discussionmentioning

confidence: 92%

“…Subsequently, several laboratories have independently examined the expression of caveolin-1 (Horiguchi et al, 2004;Joo et al, 2004;Phuoc et al, 2007) or activated AKT/ mTOR/S6 (Lin et al, 2006;Pantuck et al, 2007;Robb et al, 2007) in RCC. However, none has yet examined the expression of these pathways together.…”

mentioning

confidence: 99%

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

et al. 2008

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“…Caveolin 1 has been demonstrated to have a suppressing and promoting role in pancreatic cancer, lung cancer, esophageal squamous cell carcinoma, renal cell carcinoma, prostate cancer and melanoma (6)(7)(8)(12)(13)(14). Previous studies have found that patients with a high caveolin 1 expression have more progressive diseases, and caveolin 1 has been demonstrated to have tumor promoting and pro-survival functions in more advanced disease stages (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…However, caveolin 1 has also been demonstrated to have a tumor promoting role in prostate cancer, renal cancer and esophageal squamous cell carcinoma (6)(7)(8), suggesting that whether caveolin 1 acts as tumor suppressor or facilitator depends upon specific tumor types.…”

Section: Introductionmentioning

confidence: 99%

Caveolin 1 knockdown inhibits the proliferation, migration and invasion of human breast cancer BT474 cells

Wang

Guo

et al. 2014

Molecular Medicine Reports

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Abstract. Previous studies have demonstrated that caveolin 1 acts as a tumor suppressor in breast cancer, however, few studies have demonstrated that caveolin 1 also serves as a tumor promoter in breast cancer. In the present study, caveolin 1 small interfering RNA was used to knock down caveolin 1 expression in order to investigate the association between caveolin 1 and the proliferation and metastatic abilities of human breast cancer BT474 cells. The results revealed that cell proliferation, migration and invasion were attenuated by caveolin 1 knockdown in BT474 cells. Furthermore, caveolin 1 knockdown in BT474 cells arrested cells in the G0/G1 phase and decreased the number of cells in the S phase. In addition, caveolin 1 knockdown decreased the activation of the extracellular signal-regulated kinase 1/2 pathway and inhibited the expression of cell cycle-associated proteins (cyclin D1, c-Fos and β-catenin), whilst the expression of E-cadherin was increased. Furthermore, the protein expression of matrix metalloproteinase-2, -9 and -1 was also inhibited by caveolin 1 knockdown. In combination, these results demonstrated that caveolin 1 knockdown had a tumor suppressing effect on BT474 cells.

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“…18 Caveolin expression, shown to be a marker of unfavorable prognosis, seems to be associated with a higher vascular density as well. 17 …”

Section: Angiogenesismentioning

confidence: 99%

Genomics of renal cell cancer — Does it provide breakthrough?

Kopper

Tı́már

2006

Pathol. Oncol. Res.

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Increased expression of caveolin‐1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma

Cited by 138 publications

References 29 publications

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

Caveolin 1 knockdown inhibits the proliferation, migration and invasion of human breast cancer BT474 cells

Genomics of renal cell cancer — Does it provide breakthrough?

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