Functional Mechanisms for Human Tumor Suppressors

Sun, Wanpeng; Yang, Jian

doi:10.7150/jca.1.136

Cited by 81 publications

(65 citation statements)

References 56 publications

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“…Our results and the review of literature make us to hypothesize that GPER is a potential tumor suppressor. Tumor suppressors are known to be inactivated during cancer progression [32] which was also observed for GPER-1. The decreased expression of GPER-1 benign and malignant ovarian tumors corroborates the presumption that GPER-1 might be a tumor suppressor.…”

Section: Discussionmentioning

confidence: 82%

GPER-1 acts as a tumor suppressor in ovarian cancer

Seiz¹,

Ignatov²,

Weißenborn³

et al. 2014

Geburtshilfe Frauenheilkd

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Background: It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells. Patients and methods: GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth. Results: GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3. Conclusion: GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer.

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Section: Discussionmentioning

confidence: 82%

GPER-1 acts as a tumor suppressor in ovarian cancer

Seiz¹,

Ignatov²,

Weißenborn³

et al. 2014

Geburtshilfe Frauenheilkd

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“…Carcinogenesis is commonly regarded as a multistep process, to which aberrant polarity signaling can contribute as one of multiple causative factors (Sherr, 2004;Sun and Yang, 2010;Ellenbroek et al, 2012). In this light, carcinogenesis subsequent to the combined loss of different functions of one and the same factor is an astonishing and thus far unrecognized variation of this common concept.…”

Section: Discussionmentioning

confidence: 99%

“…Most tumor suppressors affect one or more of these processes in a cell-autonomous manner, being produced by and acting within the tumor precursor cells themselves (Sherr, 2004;Sun and Yang, 2010), whereas comparably few genes are known to block tumorigenesis in a non-cell-autonomous manner (Chua et al, 2014). Tumor suppressors often act by inhibiting or antagonizing proto-oncogenic factors.…”

Section: Introductionmentioning

confidence: 99%

509 Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

Hatzold

Beleggia

Herzig

et al. 2016

Journal of Investigative Dermatology

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The molecular pathways underlying tumor suppression are incompletely understood.Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFkB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression.

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“…), or by promoting DNA-damage repair (Kada & Shimoi, 1987). Moreover, blocking the proliferation of transformed cells has been found to be a possible mechanism for inhibiting cancer development and progression (Sun and Yang, 2010). Curcumin, epigallocatechin gallate, resveratrol, and sulforaphane are examples of natural compounds possessing interesting chemopreventive properties (Shu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Antimutagenic and antioxidant activity of a protein fraction from aerial parts ofUrtica dioica

Sotto

Mazzanti

Savickienė

et al. 2014

Pharmaceutical Biology

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Context: Urtica dioica L. (Urticaceae), stinging nettle, has been employed as a folklore remedy for a wide spectrum of ailments, including urinary disorders, prostatic hyperplasia, and liver diseases. It has been also used traditionally for cancer treatment. Object: To evaluate the potential chemopreventive properties of a protein fraction from the aerial part of Urtica dioica (namely UDHL 30 ). Materials and methods: UDHL 30 has been tested for the antimutagenic activity in bacteria (50-800 mg/plate; Ames test by the preincubation method) and for the cytotoxicity on human hepatoma HepG2 cells (0.06-2 mg/mL; 24 and 48 h incubation). Moreover, the antioxidant activity of UDHL 30 (0.1-1200 mg/mL; ABTS and superoxide-radical scavenger assays) was evaluated as potential protective mechanisms. Results: UDHL 30 was not cytotoxic on HepG2 cells up to 2 mg/mL; conversely, it exhibited a strong antimutagenic activity against the mutagen 2-aminoanthracene (2AA) in all strains tested (maximum inhibition of 56, 78, and 61% in TA98, TA100, and WP2uvrA strains, respectively, at 800 mg/plate). In addition, a remarkable scavenging activity against ABTS radical and superoxide anion (IC 50 values of 19.9 ± 1.0 mg/mL and 75.3 ± 0.9 mg/mL, respectively) was produced. Discussion and conclusions: UDHL 30 possesses antimutagenic and radical scavenging properties. Being 2AA a pro-carcinogenic agent, we hypothesize that the antimutagenicity of UDHL 30 can be due to the inhibition of CYP450-isoenzymes, involved in the mutagen bioactivation. The radical scavenger ability could contribute to 2AA-antimutagenicity. These data encourage further studies in order to better define the potential usefulness of UDHL 30 in chemoprevention.

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Functional Mechanisms for Human Tumor Suppressors

Cited by 81 publications

References 56 publications

GPER-1 acts as a tumor suppressor in ovarian cancer

GPER-1 acts as a tumor suppressor in ovarian cancer

509 Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

Antimutagenic and antioxidant activity of a protein fraction from aerial parts ofUrtica dioica

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