The tumor suppressor tuberin regulates mitotic onset through the cellular localization of cyclin B1

Silva, Elizabeth Fidalgo da; Ansari, Shora B.; Maimaiti, Jiamila; Barnes, Elizabeth A.; Kong-Beltran, Monica; Donoghue, Daniel J.; Porter, Lisa A.

doi:10.4161/cc.10.18.17296

Cited by 14 publications

(39 citation statements)

References 37 publications

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“…For example, cyclin A preferentially localizes in the nucleus, (28) while cyclin B1 accumulates in cytoplasm and translocates to the nucleus. (29) Cyclin F has been previously shown to localize in the nucleus. (14,16) However, cyclin F has been shown to partially localize in cytoplasm where it was interwoven with c-tubulin.…”

Section: Discussionmentioning

confidence: 99%

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Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis

Qiu

Cai

et al. 2013

Cancer Science

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Cyclin F, capable of forming Skp1‐Cul1‐F‐box protein ubiquitin ligase complex, is implicated in controlling centrosome duplication and preventing genome instability. Cyclin F oscillates during cell cycle with a similar pattern to cyclin A. However, its expression and significance in cancer remain obscure. In this study, we showed that cyclin F was noticeably decreased in 16 pairs of tissue samples of hepatocellular carcinoma (HCC) compared to paracarcinoma tissues, at both mRNA and protein levels. Immunohistochemical staining data revealed that in 71.8% (176/245) of HCC cases, cyclin F expression in tumor tissue was much lower than that in nontumorous tissue. Low cyclin F expression, defined by receiver operating characteristic curve analysis, was present in 69.0% of HCC patients. Low expression of cyclin F was significantly correlated with tumor size, clinical stage, serum alpha‐fetoprotein level and tumor multiplicity. Further study showed that cyclin F expression was reversely associated with tumor differentiation in HCC. Kaplan–Meier analysis indicated that low cyclin F expression was related to poor overall survival and recurrence‐free survival. The prognostic impact of cyclin F was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low cyclin F expression was an independent poor prognostic marker for overall survival. We conclude that cyclin F is downregulated in HCC and is a promising prognostic marker for patients suffering from this deadly disease.

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Section: Discussionmentioning

confidence: 99%

“…Under normal circumstances, cyclins have distinct patterns of subcellular localization. For example, cyclin A preferentially localizes in the nucleus, while cyclin B1 accumulates in cytoplasm and translocates to the nucleus . Cyclin F has been previously shown to localize in the nucleus .…”

Section: Discussionmentioning

confidence: 99%

Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis

Qiu

Cai

et al. 2013

Cancer Science

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“…Targeting the EGFR/Ras/PI3K/Akt/mTORC1 pathway is a key anticancer and anti-aging approach. There are many sites which are frequently mutated or aberrantly expressed and are being targeted in this pathway, from upstream receptors (e.g., EGFR, HER2) 25,27,28,123,124 to downstream signaling proteins such as Ras, 29,125,126 PI3K, 26,30,[127][128][129][130][131][132][133][134][135][136][137][138] PTEN, 43,139,140 Akt, [25][26][27][28] TSC1/ TSC2, [44][45][46][47]144 Rheb, [25][26][27][28]145 mTOR [25][26][27][28][146][147][148][149][150]…”

Section: Methodsmentioning

confidence: 99%

“…27,28 These include two major classes of genes, the oncogenes [29][30][31][32][33] and the tumor-suppressor genes such as retinoblastoma (RB), [34][35][36][37] TP53, [38][39][40] BRCA1, 41,42 PTEN, 43 TSC1 and TSC2. [44][45][46][47] Many of these oncogenes and tumor suppressors are often critical regulators of cellular senescence. [48][49][50][51][52][53] Moreover, microRNAs (miR-NAs) [54][55][56][57][58][59][60] and epigenetic modifications [61][62][63] have been shown to play important roles in regulating cancer progression.…”

Section: Ectopic Ngal Expression Can Alter Sensitivity Of Breast Cancmentioning

confidence: 99%

Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl-2, CaM-K inhibitors and the plant natural product berberine

et al. 2012

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Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family and has diverse roles. NGAL can stabilize matrix metalloproteinase-9 from autodegradation. NGAL is considered as a siderocalin that is important in the transport of iron. NGAL expression has also been associated with certain neoplasias and is implicated in the metastasis of breast cancer. In a previous study, we examined whether ectopic NGAL expression would alter the sensitivity of breast epithelial, breast and colorectal cancer cells to the effects of the chemotherapeutic drug doxorubicin. While abundant NGAL expression was detected in all the cells infected with a retrovirus encoding NGAL, this expression did not alter the sensitivity of these cells to doxorubicin as compared with empty vector-transduced cells. We were also interested in determining the effects of ectopic NGAL expression on the sensitivity to small-molecule inhibitors targeting key signaling molecules. Ectopic NGAL expression increased the sensitivity of MCF-7 breast cancer cells to EGFR, Bcl-2 and calmodulin kinase inhibitors as well as the natural plant product berberine. Furthermore, when suboptimal concentrations of certain inhibitors were combined with doxorubicin, a reduction in the doxorubicin IC 50 was frequently observed. An exception was observed when doxorubicin was combined with rapamycin, as doxorubicin suppressed the sensitivity of the NGAL-transduced MCF-7 cells to rapamycin when compared with the empty vector controls. In contrast, changes in the sensitivities of the NGAL-transduced HT-29 colorectal cancer cell line and the breast epithelial MCF-10A cell line were not detected compared with empty vector-transduced cells. Doxorubicin-resistant MCF-7/Dox (R) cells were examined in these experiments as a control drug-resistant line; it displayed increased sensitivity to EGFR and Bcl-2 inhibitors compared with empty vector transduced MCF-7 cells. These results indicate that NGAL expression can alter the sensitivity of certain cancer cells to small-molecule inhibitors, suggesting that patients whose tumors exhibit elevated NGAL expression or have become drug-resistant may display altered responses to certain small-molecule inhibitors.

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“…Hence, this is a valuable tool for measuring the length of G2 up to the metaphase-anaphase transition. However, the Cyclin B1 region used in this system also includes the cytoplasmic retention sequence (CRS) domain of the protein, a region known to interact with a number of intracellular proteins (Fidalgo da Silva et al 2011Hagting et al 1998;Barnes et al 2001). This poses potential problems for researchers studying or manipulating these specific proteins as the reporter may interact with their proteins of interest and may cause unexpected side effects.…”

Section: Introductionmentioning

confidence: 99%

Derivation of a novel G2 reporter system

2014

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Progression through G2 phase of the cell cycle is a technically difficult area of cell biology to study due to the lack of physical markers specific to this phase. The FUCCI system uses the biology of the cell cycle to drive fluorescence in select phases of the cell cycle. Similarly, a commercially available system has used a fluorescent analog of the Cyclin B1 protein to visualize cells from late S phase to the metaphase-anaphase transition. We have modified these systems to use the promoter and destruction box elements of Cyclin B1 to drive a cyan fluorescent protein. We demonstrate here that this is a useful tool for measuring the length of G2 phase without perturbing any aspect of cell cycle progression.

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The tumor suppressor tuberin regulates mitotic onset through the cellular localization of cyclin B1

Cited by 14 publications

References 37 publications

Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis

Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis

Ectopic NGAL expression can alter sensitivity of breast cancer cells to EGFR, Bcl-2, CaM-K inhibitors and the plant natural product berberine

Derivation of a novel G2 reporter system

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