| RRC ID |
47460
|
| Author |
Chanmee T, Ontong P, Izumikawa T, Higashide M, Mochizuki N, Chokchaitaweesuk C, Khansai M, Nakajima K, Kakizaki I, Kongtawelert P, Taniguchi N, Itano N.
|
| Title |
Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling.
|
| Journal |
J Biol Chem
|
| Abstract |
Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), an HBP rate-limiting enzyme, resembled the results of HA overproduction with regard to HIF-1α accumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling.
|
| Volume |
291(46)
|
| Pages |
24105-24120
|
| Published |
2016-11-11
|
| DOI |
10.1074/jbc.M116.751263
|
| PII |
S0021-9258(20)34680-9
|
| PMID |
27758869
|
| PMC |
PMC5104936
|
| MeSH |
Animals
Female
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Hexosamines / biosynthesis*
Hexosamines / genetics
Hyaluronic Acid / biosynthesis*
Hyaluronic Acid / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Mammary Neoplasms, Experimental / genetics
Mammary Neoplasms, Experimental / metabolism*
Mammary Neoplasms, Experimental / pathology
Mice
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Nitrogenous Group Transferases / genetics
Nitrogenous Group Transferases / metabolism
Signal Transduction*
|
| IF |
4.238
|
| Times Cited |
29
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
AxCANCre (RDB01748) |
