Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships

Park, Kwang Hwa; Choi, Sung‐E; Eom, Minseob; Kang, Yup

doi:10.1186/bcr978

Cited by 39 publications

(40 citation statements)

References 45 publications

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“…described in colon and breast cancer (21,22). These data and our observations suggest that suppression of activity of APC/C-Cdh1 is likely to be a component of neoplastic transformation or an enabling mechanism without which cancer cannot proceed.…”

Section: Discussionsupporting

confidence: 54%

E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation

Almeida

Bolaños

Moncada

2009

Proc. Natl. Acad. Sci. U.S.A.

153

132

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Cell proliferation is known to be accompanied by activation of glycolysis. We have recently discovered that the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1, which also degrades cell-cycle proteins. We now show in two different cell types (neoplastic and nonneoplastic) that both proliferation and aerobic glycolysis are prevented by overexpression of Cdh1 and enhanced by its silencing. Furthermore, we have coexpressed Cdh1 with PFKFB3-either wild-type or a mutant form resistant to ubiquitylation by APC/C-Cdh1-or with the glycolytic enzyme 6-phosphofructo-1-kinase and demonstrated that whereas glycolysis is essential for cell proliferation, its initiation in the presence of active Cdh1 does not result in proliferation. Our experiments indicate that the proliferative response, regardless of whether it occurs in normal or neoplastic cells, is dependent on a decrease in the activity of APC/ C-Cdh1, which activates both proliferation and glycolysis. These observations have implications for cell proliferation, neoplastic transformation, and the prevention and treatment of cancer.aerobic glycolysis | cell cycle | PFKFB3 | cancer

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Section: Discussionsupporting

confidence: 54%

E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation

Almeida

Bolaños

Moncada

2009

Proc. Natl. Acad. Sci. U.S.A.

153

132

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“…First, genomic aberrations in hPTTG1 (promoter mutations, amplification) have as yet not been detected, or do not play a major role in the enhanced transcription or insufficient degradation of securin. 29 Second, somatic mutations in one or more components of APC have been reported in breast 30 and colon cancer, 31 suggesting that the cause of securin overexpression in these cancers is due to insufficient degradation. Although the predominant cytoplasmic localisation of securin in melanomas as well as in other neoplasms 5 is in agreement with this hypothesis, mutations affecting APC genes (APC3, APC6 and APC8) have not been found in a number of melanoma cell lines (A Puisieux, personal communication, Lyon, France).…”

Section: Discussionmentioning

confidence: 99%

Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

et al. 2006

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Human pituitary tumour-transforming gene 1 or hPTTG1 is a proto-oncogene that codes for securin, a protein involved in sister chromatid separation. Based on previous microarray data, we studied the expression of hPTTG1/securin in melanocytic lesions. In contrast to nevi and radial growth phase melanomas, securin was expressed by scattered cells in the vertical growth phase, suggesting a role in tumour progression. In a series of 29 nodular and 29 superficial spreading melanomas, matched for all histological prognostic parameters, securin expression was significantly correlated with the nodular subtype (P ¼ 0.018) and not related to thickness. In other cancers, hPTTG1 is involved in various oncogenic pathways, including induction of neovascularisation and aneuploidy, and inhibition of p53 activity. We found coexpression of securin with wildtype p53 in the same neoplastic cells in a minority of melanomas. Expression of securin was significantly correlated with the extent of aneuploidy but not with basic fibroblast growth factor immunoreactivity or microvessel density. DNA cytometry revealed that nuclei-overexpressing securin frequently showed tetraploidy or aneuploidy. Our data show that hPTTG1 is frequently overexpressed in nodular melanoma, and suggest that hPTTG1 may act as an oncogene in the vertical growth phase, either by inhibiting anaphase, thereby causing aneuploidy and genomic instability, or by modulating the function of p53, thereby impairing apoptosis.

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“…(Peters, 2002). Given their key roles in cell cycle regulation, it is perhaps not surprising that many APC substrates have been implicated as oncogenes (Park et al, 2005).…”

Section: Introductionmentioning

confidence: 99%