The absence of LPA receptor 2 reduces the tumorigenesis by Apc^Min mutation in the intestine

Abstract

Lin S, Lee S, Shim H, Chun J, Yun CC. The absence of LPA receptor 2 reduces the tumorigenesis by Apc Min mutation in the intestine.

Regulation of Hypoxia-inducible Factor 1α (HIF-1α) by Lysophosphatidic Acid Is Dependent on Interplay between p53 and Krüppel-like Factor 5

“…LPA Induces HIF-1␣ Expression-We have shown previously that exposing HCT116 cells to LPA overnight results in increased HIF-1␣ expression under normoxic conditions (16). Fig.…”

“…Moreover, hypoxia enhances the effects of LPA on VEGF expression and the metastasis of ovarian cancer cells (20,21). We observed previously that loss of LPA 2 function results in decreased HIF-1␣ expression in intestinal tumors (16). Similarly, mouse embryos lacking LPA-generating autotaxin lack HIF-1␣ expression, and the absence of HIF-1␣ is independent of oxygen tension (22).…”

“…qRT-PCR was performed as described (16). The following primer pairs were used for HIF-1␣: 5Ј-CACTACCACTGCCACCACTG-3Ј and 5Ј-CCTTTTCCTGCTCTGTTTGG-3Ј.…”

“…LPA 2 -deficient intestinal tumors show reduced expression levels of cyclooxygenase 2, ␤-catenin, and Krüppel-like factor 5 (KLF5) (16,17). It has been shown that LPA stimulates vascular endothelial growth factor (VEGF) expression, whereas transgenic expression of LPA 2 in mouse ovaries produces VEGF and urokinase-type plasminogen activator (18,19).…”

Lysophosphatidic Acid Activates Lipogenic Pathways and de Novo Lipid Synthesis in Ovarian Cancer Cells

“…There is also strong evidence from xenograft mouse models and transgenic mice that LPA 2 is more oncogenic compared with LPA 1 and LPA 3 (17,59). The compelling evidence for the implication of LPA 2 as an oncogene stems from recent studies by Yun and co-workers (18,60) who showed that LPA 2 -deficient mice were more resistant to intestinal tumorigenesis induced by colitis or by ApcMin mutation. However, the molecular mechanisms for the oncogenic activity of LPA 2 are not well understood.…”