Rho GTPases: Regulation and roles in cancer cell biology

Haga, Raquel Brandão; Ridley, Anne J.

doi:10.1080/21541248.2016.1232583

Cited by 378 publications

(397 citation statements)

References 171 publications

(195 reference statements)

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“…For example, DNM2 enzymatic activity and proper intra-cellular localization are required for extracellular matrix degradation by invasive cancer cells31. DNM2 is required for the endocytosis of several proteins associated with cancer motility and invasiveness3233 and for endocytosis of several oncogenic receptors3435. Furthermore, DNM2 regulates Golgi structure and vesiculation during the secretory process which can affect trafficking of other carcinogenic signaling molecules36.…”

Section: Discussionmentioning

confidence: 99%

Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute Lymphoblastic Leukemia

Han

et al. 2016

Sci Rep

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Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression in other types of ALL are not reported. We studied DNM2 mRNA level in adults with B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals in both forms of ALL. High DNM2 expression is associated with some clinical and laboratory features, inferior outcomes and with leukaemia cell proliferation. We also found Ikaros directly binds the DNM2 promoter and suppresses DNM2 expression. Consequently IKZF1 deletion is associated with high DNM2 expression. Conversely, casein kinase-2 (CK2)-inhibitor increases Ikaros function thereby inhibiting DNM2 expression. Inhibiting DNM2 suppresses proliferation of leukemia cells and synergizes with CK2 inhibition. Our data indicate high DNM2 expression is associated with Ikaros dysregulation and may be important in the development of B-ALL.

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Section: Discussionmentioning

confidence: 99%

Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute Lymphoblastic Leukemia

Han

et al. 2016

Sci Rep

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“…[1][2][3][4][5] Abnormal GTPase activities are significant in the etiology of many human diseases. [6][7][8] In mammalian oocytes, many members of GTPase superfamily have been identified to be involved in meiosis progression. Ran GTPase has been reported to regulate the polarized activation of Cdc42, which will than promote polar body protrusion and asymmetric division.…”

Section: Introductionmentioning

confidence: 99%

GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes

Zhou

Shi

et al. 2017

Cell Cycle

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Meiotic failure in oocytes is the major determinant of human zygote-originated reproductive diseases, the successful accomplishment of meiosis largely relay on the normal functions of many female fertility factors. Elmod2 is a member of the Elmod family with the strongest GAP (GTPase-activating protein) activity; although it was identified as a possible maternal protein, its actual physiologic role in mammalian oocytes has not been elucidated. Herein we reported that among Elmod family proteins, Elmod2 is the most abundant in mouse oocytes, and that inhibition of Elmod2 by specific siRNA caused severe meiotic delay and abnormal chromosomal segregation during anaphase. Elmod2 knockdown also significantly decreased the rate of oocyte maturation (to MII, with first polar body extrusion), and significantly greater numbers of Elmod2-knockdown MII oocytes were aneuploid. Correspondingly, Elmod2 knockdown dramatically decreased fertilization rate. To investigate the mechanism(s) involved, we found that Elmod2 knockdown caused significantly more abnormal mitochondrial aggregation and diminished cellular ATP levels; and we also found that Elmod2 co-localized and interacted with Arl2, a GTPase that is known to maintain mitochondrial dynamics and ATP levels in oocytes. In summary, we found that Elmod2 is the GAP essential to meiosis progression of mouse oocytes, most likely by regulating mitochondrial dynamics.

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“…In the present study, 3-(4-acetyl-phenyl)-1H-quinazolin-2,4-dione 1 was utilized as a starting compound for the synthesis of the quinazolindione skeletons (2)(3)(4)(5)(6)(7)(8)(9). The computational methodologies like homology modeling, active site prediction, and virtual screening approach have been developed for hit identification against cancer.…”

Section: Resultsmentioning

confidence: 99%

“…[4,5] The biochemical pathway represented in Figure 1 represents that Rho7 protein acts as a controller of certain processes such as regulation of actin cytoskeleton in response to extracellular growth factor. [6] Mutation in Rho7 protein was identified as possible pathogenic in patients with breast cancer cell lines (MCF-7) and hepatocellular cancer cell lines (HepG2). [5] The quinazolindione scaffold and its derivatives have gained a wide spectrum in the medicinal and pharmaceutical chemistry fields, [7][8][9] due to their promising biological activities like antifungal, antibacterial, and anticancer.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, in vitro biological evaluation and in silico docking studies of new quinazolin‐2,4‐dione analogues as possible anticarcinoma agents

Abdelmonsef

Mosallam

2020

Journal of Heterocyclic Chem

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Today, cancer is considered as one of the major reasons of death in human beings worldwide. We reported herein the synthesis, anticancer activity, and in silico docking studies of a series of nine quinazolindione‐based scaffolds bearing pyrimidine, pyridine, pyran, and pyrazole moieties (1‐9) through Michael addition, Vilsmeier‐Haack, Claisen‐Schmidt, and nucleophilic addition reactions. The chemical structures of the newly prepared compounds were ascertained by means of their spectral analysis techniques like IR, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, mass spectroscopy, and elemental analysis. This work was conducted to investigate the implication of Rho7 protein in breast and hepatocellular cancer cells aggressively. MCF‐7 and HepG2 cells have been selected as models for the effect of protein expression on breast and hepatocellular cancers cell growth. All prepared compounds were biologically evaluated for their antiproliferative efficacy on hepatic cancer cell lines (HepG2) and breast cancer cell lines (MCF‐7); also, their effects on normal cell lines (BALB/3T3) were studied. Moreover, in silico molecular docking studies were studied for the compounds against the binding site of Homo sapiens Rho7 protein. The pharmacokinetic properties of the newer compounds were also evaluated using various computational tools. The compounds showed interesting interactions with satisfactory docking scores to the target Rho7; thus, they may act as promising potent drug candidates against cancer.

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Rho GTPases: Regulation and roles in cancer cell biology

Cited by 378 publications

References 171 publications

Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute Lymphoblastic Leukemia

Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute Lymphoblastic Leukemia

GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes

Synthesis, in vitro biological evaluation and in silico docking studies of new quinazolin‐2,4‐dione analogues as possible anticarcinoma agents

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