Role of LKB1-CRTC1 on glycosylated COX-2 and response to COX-2 inhibition in lung cancer.

@article{Cao2015RoleOL,
  title={Role of LKB1-CRTC1 on glycosylated COX-2 and response to COX-2 inhibition in lung cancer.},
  author={Chunxia Cao and Ruli Gao and Min Zhang and Antonio L. Amelio and Mohammad Fallahi and Zirong Chen and Yu-mei Gu and Chengbin Hu and Eric A. Welsh and Brienne E. Engel and Eric B. Haura and W Douglas Cress and Lizi Wu and Maria Zajac-Kaye and Frederic J Kaye},
  journal={Journal of the National Cancer Institute},
  year={2015},
  volume={107 1},
  pages={
          358
        }
}
  • C. Cao, Ruli Gao, +12 authors F. Kaye
  • Published 2015
  • Biology, Medicine
  • Journal of the National Cancer Institute
BACKGROUND Cyclooxygenase-2 (COX-2) directs the synthesis of prostaglandins including PGE-2 linking inflammation with mitogenic signaling. COX-2 is also an anticancer target, however, treatment strategies have been limited by unreliable expression assays and by inconsistent tumor responses to COX-2 inhibition. METHODS We analyzed the TCGA and Director's Challenge lung cancer datasets (n = 188) and also generated an LKB1-null lung cancer gene signature (n = 53) to search the Broad Institute… Expand
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References

SHOWING 1-10 OF 40 REFERENCES
Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection.
TLDR
Understanding the conditions under which multiple EP2 signaling pathways are engaged might suggest novel therapeutic strategies to target this key inflammatory prostaglandin receptor. Expand
Altered LKB1/CREB-regulated transcription co-activator (CRTC) signaling axis promotes esophageal cancer cell migration and invasion
TLDR
Mechanistically, it is determined that CRTC signaling becomes activated because of LKB1 loss, which results in the transcriptional activation of specific downstream targets including LYPD3, a critical mediator for L KB1 loss-of-function. Expand
Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells.
TLDR
Administration of dmPGE2 to growing PC-3 cells significantly increased cellular proliferation, total DNA content and endogenous PGE2 concentration, and increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. Expand
LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin.
TLDR
Phenformin is suggested as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors, resulting in prolonged survival in these tumors. Expand
Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice.
TLDR
Results are consistent with the hypothesis that COX-2 inhibitors suppress growth of gastric cancer xenografts mainly by inducing apoptosis and suppressing replication of the neoplastic cells. Expand
Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition
TLDR
Characterization of the two COX isozymes is allowing the discrimination of the roles each play in physiological processes such as homeostatic maintenance of the gastrointestinal tract, renal function, blood clotting, embryonic implantation, parturition, pain, and fever. Expand
Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice
TLDR
It is shown that homozygous deletion of the gene encoding a cell-surface receptor of PGE2, EP2, causes decreases in number and size of intestinal polyps in ApcΔ716 mice (a mouse model for human familial adenomatous polyposis), and that increased cellular cAMP stimulates expression of more COX-2 and vascular endothelial growth factor in the polyp stroma. Expand
Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer
TLDR
The role of dysregulated Crtc as a bona fide cancer gene is strengthened, a new element to the complex LKB1 tumorigenic axis is presented, and Crtc genes may be aberrantly activated in a wider range of common adult malignancies. Expand
Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention.
TLDR
Evidence is presented that cyclooxygenase-2 and epidermal growth factor receptor (EGFR) are potential pharmacologic targets to prevent cancer and key data implicating a causal relationship between COX-2, EGFR, and carcinogenesis are reviewed. Expand
Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2.
TLDR
These data establish a role for COX-2 in promoting Peutz-Jeghers polyposis and suggest that COx-2 chemoprevention may prove beneficial in the treatment of PJS. Expand
...
1
2
3
4
...