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p21-activated kinases in cancer
TLDR
Paks are well-known regulators of cytoskeletal remodelling and cell motility, but have recently been shown to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, which results in tumour formation and cell invasiveness.
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The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor α to the plasma membrane
TLDR
This study examined how E2 causes ERα to translocate to the region of the plasma membrane and focused on mechanisms whereby Shc and the insulin-like growth factor-1 receptor (IGF-1R) mediate this process.
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Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity
TLDR
It is shown that the antitumor and antiangiogenic activity of VEGFR inhibitors is dependent on steady-state concentration of the compound above a threshold, which is consistent with the concentration required for the inhibition of V EGF-induced V EGFR2 phosphorylation in mouse lungs.
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Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.
TLDR
In immune-compromised mice implanted with human BT474 breast carcinoma xenografts, a single i.p. administration of GSK690693 inhibited GSK3 beta phosphorylation in a dose- and time-dependent manner and showed reductions in phosphorylated Akt substrates in vivo.
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Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2.
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Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor
TLDR
Results identify ER-mediated transcription as a nuclear target of MTA1 and indicate that HDAC complexes associated with the MTA1 corepressor may mediate ER transcriptional repression by HRG.
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Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1
TLDR
The results indicate that FLNa may be essential for Pak1-induced cytoskeletal reorganization and that the two-way regulatory interaction between Pak1 and FLNa might contribute to the local stimulation of Pak1 activity and its targets in cytoskeleton structures.
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Overexpression of tissue transglutaminase leads to constitutive activation of nuclear factor-kappaB in cancer cells: delineation of a novel pathway.
TLDR
TG2 induces constitutive activation of NF-kappaB in tumor cells via a novel pathway that is most likely independent of I kappaB alpha kinase, therefore, TG2 may be an attractive alternate target for inhibiting constitutive NF-KappaB activation and rendering cancer cells sensitive to anticancer therapies.
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Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity.
TLDR
A first-in-class, small molecule inhibitor of the eukaryotic initiation factor 2-alpha kinase 3 (EIF2AK3) or PERK, one of the three mediators of UPR signaling, is identified and development of any PERK inhibitor in human subjects would need to be cautiously pursued in cancer patients.
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Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation.
TLDR
E2 rapidly induced Shc phosphorylation and Shc-Grb2 (growth factor receptor binding protein 2)-Sos (son of sevenless) complex formation in MCF-7 cells and ERalpha can mediate the rapid effects of E2 on Shc, MAPK, Elk-1, and morphological changes in breast cancer cells.
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