Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors

Williams, Catherine J.; Mitsiades, Nicholas; Sozopoulos, Elias; Hsi, Alex; Wolk, Alicja; Nifli, Artemissia-Phoebe; Tseleni‐Balafouta, Sofia; Mantzoros, Christos S.

doi:10.1677/erc-07-0197

Cited by 76 publications

(58 citation statements)

References 42 publications

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“…A recent study has reported higher levels of adiponectin receptors in colorectal carcinomas versus nontumor specimens (Williams et al 2008). In another investigation, AdipoR1 expression tended to be more pronounced in breast malignant cells than normal tissue (Korner et al 2007).…”

Section: Discussionmentioning

confidence: 87%

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Jardé

Caldefie-Chézet

Goncalves-Mendès

et al. 2009

Endocrine-Related Cancer

135

121

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Obesity is a risk factor for breast cancer development. A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development. This prompted us to investigate the role of adiponectin and leptin in mammary carcinogenesis. Adiponectin receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rt, representing all the isoforms of Ob-R) proteins were detected by immunohistochemistry in in situ ductal carcinoma, invasive ductal malignancy, and healthy adjacent tissue. In addition, mRNA expression of adiponectin, AdipoR1, AdipoR2, leptin, Ob-Rt, and Ob-Rl (the long isoform of Ob-R) was observed in MCF-7 breast cancer cells. Interestingly, leptin mRNA expression was 34.7-fold higher than adiponectin mRNA expression in the MCF-7 cell line. Moreover, adiponectin (10 mg/ml) tended to decrease the mRNA expression of leptin (K36%) and Ob-Rl (K28%) and significantly decreased Ob-Rt mRNA level (K26%). In contrast, leptin treatment (1 mg/ml) significantly decreased AdipoR1 mRNA (K23%). Adiponectin treatment (10 mg/ml) inhibited the proliferation of MCF-7 cells, whereas leptin (1 mg/ml) stimulated the growth of cancer cells. In addition, adiponectin inhibited leptin-induced cell proliferation (both 1 mg/ml). Using microarray analysis, we found that adiponectin reduced the mRNA levels of genes involved in cell cycle regulation (mitogen-activated protein kinase 3 and ATM), apoptosis (BAG1, BAG3, and TP53), and potential diagnosis/prognosis markers (ACADS, CYP19A1, DEGS1, and EVL), whereas leptin induced progesterone receptor mRNA expression.In conclusion, the current study indicates an interaction of leptin-and adiponectin-signaling pathways in MCF-7 cancer cells whose proliferation is stimulated by leptin and suppressed by adiponectin.

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Section: Discussionmentioning

confidence: 87%

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Jardé

Caldefie-Chézet

Goncalves-Mendès

et al. 2009

Endocrine-Related Cancer

135

121

View full text Add to dashboard Cite

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“…The direct inhibitory effect of adiponectin on the growth of colorectal cancer cells (34,35), suggestive of the expression of functional adiponectin receptors in colorectal cancer cells, has been demonstrated, and previous studies using human specimens have provided evidence that AdipoR1 and AdipoR2 are expressed in colorectal cancer tissue at mRNA and protein levels (31,36,37).…”

Section: Discussionmentioning

confidence: 92%

“…In humans, AdipoR1 and AdipoR2 have been reported to be expressed in adipocytes (21), skeletal muscle cells (22), vascular smooth muscle cells, macrophages (23), pancreatic β cells (24) and liver (25,26). The expression of adiponectin receptors has also been reported in various cancer tissues (27)(28)(29)(30)(31)(32), although the results are still controversial, and the role of the receptor expression in tumor tissues remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer

Hiyoshi¹

2012

Oncol Lett

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Abstract. Adiponectin is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of tumor growth. The expression and function of the two major adiponectin receptors, AdipoR1 and AdipoR2, in malignant tissue have not been well characterized. In the present study, we evaluated the mRNA levels of AdipoR1 and AdipoR2 expression in 48 surgically resected colorectal cancer specimens, as well as normal colonic mucosa, by quantitative RT-PCR. The values obtained were standardized by β-actin mRNA, and the correlation between their relative expression levels and the clinicopathological characteristics of the patients was examined. The relative expression levels of AdipoR1 and AdipoR2 were significantly reduced in cancer tissue compared with normal tissue (AdipoR1: 0.97±0.39 vs. 1.37±0.41, P<0.0001; AdipoR2: 0.92±0.31 vs. 1.60±0.46, P<0.0001). AdipoR1 and AdipoR2 levels were further reduced in tumors with nodal metastases and the difference was statistically significant in the case of AdipoR2 (0.79±0.27 vs. 1.02±0.30, P=0.012). The results of this study demonstrated that the expression levels of adiponectin receptors are reduced in cancer specimens compared to normal tissue, indicating a downregulation in the course of the development and progression of colorectal cancer. Since adiponectin is abundantly present in the whole body and has inhibitory effects on cancer cells, this downregulation of the receptors may be an escape mechanism of malignant cells from the suppressive effects of adiponectin.

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“…We found that RKTG functions as a negative regulator of Ras to ERK signaling by sequestrating Raf kinase in the Golgi apparatus [23,24], and such regulation is likely associated with the development of cancer in mouse models [24,25]. Adiponectin receptors (PAQR1 and PAQR2), in addition to their established role in glucose and lipid metabolism [26], were also found to regulate p38 [26], JNK [27] and tumorigenesis [28][29][30]. These findings, therefore, indicate that members of the PAQR family may regulate basic cell activities through MAPK signaling pathways.…”

Section: Introductionmentioning

confidence: 88%

PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus

et al. 2011

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Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQR11 of the progestin and AdipoQ receptors family. PAQR10 and PAQR11 are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQR11 stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent manner. Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQR11 can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQR11 is in an active state. Consistently, knockdown of PAQR10 and PAQR11 reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQR11 are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQR11. The simulation of ERK phosphorylation by overexpressed PAQR10/ PAQR11 is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQR11. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11.

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Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors

Cited by 76 publications

References 42 publications

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies

Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer

PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus

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