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Simonas Daunys Vilma Petrikaitė 《Biology of the cell / under the auspices of the European Cell Biology Organization》2020,112(12):383-397
The main function of carbonic anhydrases (CAs) in cancer cells is the pH regulation through a conversion of H2O and CO2 to H+ and HCO3−. However, the data of in vitro and in vivo studies have demonstrated that transmembrane isoforms of CA IX and CA XII are involved in various steps of cancer cell migration, invasion and metastasis. According to literature, inhibition of these CAs can affect the expression of multiple proteins. Some scientific groups have reported the possible interactions between CA IX and E-cadherin–catenin system, CA IX and integrins, CA IX, CA XII and ion transporters, which all are highly involved in cell-to-cell adhesion, the formation of membrane protrusions and focal adhesions. Nevertheless, CA IX and CA XII have a high impact on tumour growth and metastases formation. The data discussed in this review are quite recent. It highly support the role of CA IX and CA XII in various cancer metastasis processes through their interactions to other invasion proteins. Nevertheless, all findings show the great potential of these CAs in the context of research and application in clinical use. 相似文献
43.
Nenad Bukvic Carla CesaranoCaterina Ceccarini Marianna BrunoMaria Rosaria Lipsi Maria Grazia GallicchioMaria Assunta Carboni Lucia ValenteGiulia Cotoia Raffaele Antonetti 《Gene》2013
Herein, we describe a case of an infertile man detected in postnatal diagnosis with FISH characterization and array-CGH used for genome-wide screening which allowed the identification of a complex rearrangement involving sex chromosomes, apparently without severe phenotypic consequences. The deletion detected in our patient has been compared with previously reported cases leading us to propose a hypothetical diagnostic algorithm that would be useful in similar clinical situations, with imperative multi disciplinary approach integrated with genetic counseling. Our patient, uniquely of reproductive age, is one of six reported cases of duplication of Xp22.3 (~ 8.4 Mb) segment and contemporary deletion of Yq (~ 42.9 Mb) with final karyotype as follows:
- 46,X,der(Y),t(X;Y)(Ypter → Yq11.221::Xp22.33 → Xpter).ish der(Y) (Yptel+,Ycen+,RP11-529I21+,RP11-506M9-Yqtel −,Xptel +). arrXp22.33p22.31(702–8,395,963, 8,408,289x1), Yq11.221q12 (14,569,317x1, 14,587,321–57,440,839x0) 相似文献
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Two syndromes are known to be associated with WNT7A mutations: Al-Awadi–Raas-Rothschild syndrome (AARRS) and Fuhrmann syndrome. Woods et al. (2006) showed that there is complete and partial loss of WNT7A function in these two syndromes respectively. Therefore, both syndromes have similar clinical features but the phenotype in Fuhrmann syndrome is less severe. The G204S mutation was previously reported to result in AARRS phenotype in three Saudi families. In the current communication, we report on a different unrelated Saudi patient with the same mutation but the patient had Fuhrmann syndrome phenotype. We believe this case is important because it questions the presence of a phenotype–genotype correlation in WNT7A mutations and because it demonstrates that the G204S mutation may be associated with both AARRS and Fuhrmann phenotypes. 相似文献
46.
Molecular dynamics simulations of linear models interacting through a dipolar Kihara intermolecular potential are presented. Molecular orientation correlations are used to calculate the orientational factor kappa squared in the resonance energy transfer (RET) as a function of the intermolecular separation. The distance, R 0 (2/3), at which the simulated systems show an isotropic behavior is calculated and an analysis of the dependence of R 0 (2/3) on microscopic properties (molecular aspect ratio and dipole moment) as well on thermodynamics (temperature and density) is presented. An explanation of the use of metallic cations as probes in RET is given and some relations of our models with biological molecules are pointed out. 相似文献
47.
Hiroyuki Hosokawa Phat Vinh Dip Maria Merkulova Anastasia Bakulina Zhenjie Zhuang Ashok Khatri Xiaoying Jian Shawn M. Keating Stephanie A. Bueler John L. Rubinstein Paul A. Randazzo Dennis A. Ausiello Gerhard Grüber Vladimir Marshansky 《The Journal of biological chemistry》2013,288(8):5896-5913
Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H+-ATPase (V-ATPase) with cytohesin-2, a GDP/GTP exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2, and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first 17 amino acids (a2N(1–17)), potently modulates the enzymatic GDP/GTP exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF activity via direct interaction with the Sec7 domain of cytohesin-2. The structure of a2N(1–17) and its amino acids Phe5, Met10, and Gln14 involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V-ATPase formed by its a2N(1–17) epitope competes with the switch 2 region of Arf1 and Arf6 for binding to the Sec7 domain of cytohesin-2. The amino acid sequence alignment and GEF activity studies also uncovered the conserved character of signaling between all four (a1–a4) a-subunit isoforms of mammalian V-ATPase and cytohesin-2. Moreover, the conserved character of this phenomenon was also confirmed in experiments showing binding of mammalian cytohesin-2 to the intact yeast V-ATPase holo-complex. Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor. 相似文献
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Aseel J. Marzoq Nathalia Giese J?rg D. Hoheisel Mohamed Saiel Saeed Alhamdani 《The Journal of biological chemistry》2013,288(45):32517-32527
Pancreatic stellate cells are key mediators in chronic pancreatitis and play a central role in the development of pancreatic fibrosis, stromal formation, and progression of pancreatic cancer. This study was aimed at investigating molecular changes at the level of the proteome that are associated with the activation of pancreatic stellate cells by proinflammatory factors, namely TNF-α, FGF2, IL6, and chemokine (C-C motif) ligand 4 (CCL4). They were added individually to cells growing in serum-free medium next to controls in medium supplemented with serum, thus containing a mixture of them all, or in serum-free medium alone. Variations were detected by means of a microarray of 810 antibodies targeting relevant proteins. All tested factors triggered increased proliferation and migration. Further analysis showed that TNF-α is the prime factor responsible for the activation of pancreatic stellate cells. CCL4 is associated with cellular neovascularization, whereas FGF2 and IL6 induction led to better cellular survival and decreased apoptotic activity of the stellate cells. The identified direct effects of individual cytokines on human pancreatic stellate cells provide new insights about their contribution to pancreatic cancer promotion. 相似文献