Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells

Fiucci, Giusy; Ravid, Dana; Reich, Reuven; Liscovitch, Mordechai

doi:10.1038/sj.onc.1205300

Cited by 235 publications

(199 citation statements)

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“…CAV1 has been reported to interact with various intracellular signalling pathways and is thought to suppress tumour growth in breast cancer cell lines Razani et al, 2001;Fiucci et al, 2002). Prior studies have suggested that oncogenic transformation results in reduced cellular levels of caveolin (Glenney and Soppet, 1992;Sager et al, 1994;Koleske et al, 1995), and that this reduction probably contributes to a loss of caveolae (Koleske et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer

et al. 2004

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Caveolin-1 and -2 (CAV1, CAV2) are closely linked genes localised to the fragile region of 7q31 (FRA7G), and loss of heterozygosity involving this region has been reported in breast cancer. Several studies have suggested that CAV1 is a negative regulator of HER2/ neu signal transduction in vitro. However, the clinical significance of CAV1 in breast cancer has not yet been clarified. We examined quantitatively the mRNA levels of CAV1, CAV2 and HER2/neu in 162 cases of breast cancer using real-time PCR. Caveolin-1 and -2 protein expression was also examined by Western blotting and immunohistochemistry. We then evaluated for correlations between CAV1, CAV2 and HER2/neu gene expression and clinicopathologic factors in the 162 breast cancer cases. Results showed higher HER2/neu mRMA levels and lower CAV1 and CAV2 mRMA levels in breast cancer tissues than in corresponding normal tissues (Po0.001). Caveolin-1 and -2 protein expression levels were also suppressed in cancer tissues compared to normal tissues by Western blotting. Immunohistochemistry revealed that CAV1 and CAV2 proteins were abundantly expressed in mammary gland myoepithelial cells, but only weakly in ductalepithelial cells. Reduced CAV1 mRNA level was significantly associated with increasing tumour size (P ¼ 0.041), and negative oestrogen receptor status (P ¼ 0.021). There was also a significant association between low CAV2 mRNA level and negative progesterone receptor status (P ¼ 0.013), and between high HER2/neu mRNA level and negative hormonal receptor status (ER, P ¼ 0.029, PgR, P ¼ 0.019). While there was no relationship between HER2/neu and CAV1 mRNA levels, a significant association between CAV1 and CAV2 mRNA levels was observed (Po0.001). Our results indicated that CAV1 suppression correlated closely with that of CAV2 in breast cancer, that CAV1 level was inversely correlated with tumour size, and that CAV1 and CAV2 levels were correlated with hormonal receptor status. Therefore, CAV1 and CAV2 play an important role in tumour progression in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer

et al. 2004

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“…Of interest, the interaction between caveolin-1 and EGFR results in inhibition of ERK activation, lamellipodia formation and cell migration of mammary carcinoma cells 39 and caveolin-1 expression inhibit invasiveness in the same cells. 40 The occurrence of a possible interaction between AR and caveolin-1 and the formation of a complex among AR, caveolin and EGFR is currently under investigation in our Lab. We prospect a scenario where interaction between AR and EGFR provokes a disruption of the mechanisms leading to autotransphosphorylation of the receptor and PI3K activation in response to EGF leading to decreased invasion of these cells.…”

Section: Egfr Internalization Is Altered In Pc3-ar Cellsmentioning

confidence: 99%

EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen‐sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR)

Bonaccorsi

Carloni

Muratori

et al. 2004

Intl Journal of Cancer

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We previously demonstrated that expression of androgen receptor (AR) by transfection of the androgen-independent prostate cancer cell line PC3 decreases invasion and adhesion of these cells (PC3-AR) through modulation of ␣6␤4 integrin expression. The treatment with androgens further reduced invasion of the cells without modifying ␣6␤4 expression, suggesting an interference with the invasion process by androgens. Here, we investigated EGF-mediated signal transduction processes that lead to invasion in PC3-AR cells. We show that EGF-induced EGFR autotransphosphorylation is reduced in PC3-AR cells compared to PC3 cells transfected only with the vector (PC3-Neo). EGF-stimulated PI3K activity, a key signaling pathway for invasion of these cells, and EGF-PI3K interaction are also decreased in PC3 Key words: prostate cancer; epidermal growth factor receptor; androgen receptor; PI3K; invasionProstate Cancer (PC) is one of the most common cancer and the second leading cause of death in American men. 1 Since prostate cancer cell growth is enhanced by androgens, in the advanced stages of the disease, androgen ablation therapy represents a valuable tool for the treatment of these patients. However the development in most patients after few years of treatment of androgenindependent clones, characterized by higher invasiveness and metastatic properties, has focused attention on the molecular mechanisms that lead to loss of androgen-dependence as well as on the pathways that are regulated by androgens in these cells besides proliferation. Indeed, although androgens are the major stimulus for proliferation of prostate cancer cells, maintenance of androgensensitivity appears to keep a more differentiated and less malignant phenotype of these cells. The ability to produce tumors in nude mice, for instance, is higher in androgen-insensitive cell lines (such as PC3 and DU145) with respect to androgen sensitive (LNCaP). 2 In this light, the role of androgens in the regulation of the pathways involved in invasion and metastasis represents a major task in studies on prostate cancer biology. 3 As a result, some androgen-regulated genes involved in signaling pathways that lead to invasion have been recently identified 4 -6 and their role in decreasing invasion ability of androgen-sensitive prostate cancer cells indicated. Migration and invasion of cancer cells is regulated by multiple pathways that employ various growth factor and their receptors, integrins and cytoskeletal elements. A key role is played by the EGF receptor (EGFR), which, following interaction with the integrin ␣6␤4, promotes cell migration through activation of PI3K and other downstream pathways. 7,8 In a previous study, we demonstrated that the expression of androgen receptor in PC3 cells by transfection with a full-length human androgen receptor expression vector (PC3-AR) determined a decrease in the expression of the integrin ␣6␤4 and in the ability of these cells to invade Matrigel in response to EGF. 6 The treatment with the synthetic androgen R1881 determined a ...

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“…Interestingly, caveolin-1, a principal component of caveolae membranes and a putative tumor suppressor gene (Rothberg et al, 1992;Wiechen et al, 2001;Fiucci et al, 2002), was not detected in xCT þ / þ melanocytes, but was highly expressed in xCT À/À melanocytes ( Figure 3a). Consistently, semiquantitative reverse transcription-PCR showed that quantities of caveolin-1 mRNA in xCT À/À melanocytes was also significantly higher than that in wild-type controls, suggesting that the upregulation of caveolin-1 is possibly due to its increased transcription (Figure 3b).…”

Section: Disruption Of Xct Upregulates Caveolin-1mentioning

confidence: 99%

Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/β-catenin pathway

et al. 2008

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xCT, the functional subunit of the cystine/glutamate transporter xc-system, plays a critical role in the maintenance of intracellular glutathione and redox balance. Disruption of xCT significantly inhibits the growth of a variety of carcinomas, including lymphoma, glioma, prostate and breast cancer. However, the role of xCT in tumor metastasis remains largely unknown. In this study, both xCT þ / þ and xCT À/À melanocytes were used to evaluate the role of xCT in adhesion. xCT activity was suppressed by an inhibitor, sulfasalazine (SASP), or by xCT siRNA in an esophageal cancer cell line, KYSE150. We found that disruption of xCT enhanced homotypic cell-cell adhesion and attenuated cell-extracellular matrix adhesion. SASP significantly inhibited both cell invasion of KYSE150 in vitro and its experimental metastasis in nude mice. Caveolin-1 was upregulated and b-catenin was recruited to the plasma membrane when xCT was deficient, which were followed by the inhibition of b-catenin transcriptional activity. Further study revealed that the upregulation of caveolin-1 and inhibition of tumor cell invasion were mediated by reactive oxygen species-induced p38 MAPK activation. These results first establish the role of xCT in tumor metastasis and implicate a potential target for cancer therapy.

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Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells

Cited by 235 publications

References 72 publications

Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer

Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer

EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen‐sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR)

Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/β-catenin pathway

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