TY - JOUR
T1 - Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway
T2 - Role of Palmitic Acid
AU - Kwan, Hiu Yee
AU - Fu, Xiuqiong
AU - Liu, Bin
AU - Chao, Xiaojuan
AU - Chan, Chi Leung
AU - Cao, Huihui
AU - Su, Tao
AU - Tse, Anfernee Kai Wing
AU - Fong, Wang Fun
AU - Yu, Zhi-Ling
N1 - Funding Information:
This work was supported in part by the Research Grant Council of SAR of Hong Kong under GRF (HKBU262512) and Hong Kong Baptist University Grants FRG2/13-14/016 and FRG1/13-14/062 and by Shenzhen STIC Grant JCYJ20120829154222473 (to Z.-L. Y.). This work was also supported by Research Grant Council of SAR of Hong Kong under GRF (HKBU260613) and Hong Kong Baptist University Grant FRG2/12-13/039 and FRG2/13-14/030 (to H. Y. K.).
Publisher copyright:
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/10/31
Y1 - 2014/10/31
N2 - Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study was aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared with mono-cultured melanoma. In addition, fluorescently labeled fatty acid BODIPY® FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provide fatty acids to melanoma cells. Compared with mono-cultured melanoma, co-cultured melanoma cells had a higher proliferation and phospho-Akt (Ser-473 and Thr-450) expression. Overexpression of Akt mutants in melanoma cells reduced the co-culture-enhanced proliferation. A lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation, changed the cell cycle distribution, and increased phospho-Akt (Ser-473 and Thr-450) and PI3K but not phospho-PTEN (phosphophosphatase and tensin homolog) expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significantly larger tumor in mice compared with control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid that promotes melanoma cell growth by activating Akt.
AB - Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study was aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared with mono-cultured melanoma. In addition, fluorescently labeled fatty acid BODIPY® FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provide fatty acids to melanoma cells. Compared with mono-cultured melanoma, co-cultured melanoma cells had a higher proliferation and phospho-Akt (Ser-473 and Thr-450) expression. Overexpression of Akt mutants in melanoma cells reduced the co-culture-enhanced proliferation. A lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation, changed the cell cycle distribution, and increased phospho-Akt (Ser-473 and Thr-450) and PI3K but not phospho-PTEN (phosphophosphatase and tensin homolog) expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significantly larger tumor in mice compared with control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid that promotes melanoma cell growth by activating Akt.
UR - http://www.scopus.com/inward/record.url?scp=84910092046&partnerID=8YFLogxK
U2 - 10.1074/jbc.M114.593210
DO - 10.1074/jbc.M114.593210
M3 - Journal article
C2 - 25228694
AN - SCOPUS:84910092046
SN - 0021-9258
VL - 289
SP - 30525
EP - 30537
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -