Fatty Acid Metabolism in Tumor Initiation

Fatty acid synthesis plays a pivotal role in tumor initiation and progression by providing energy and cell membrane components to rapidly growing cancer cells. De novo synthesis of lipid is quite specific to cancer cells and blocking this process induces apoptosis to them. Thus, the fatty acid synthase (FAS) is considered to be an excellent therapeutic target.

In a series of publications, we reported:

  • how FAS expression is regulated
  • what is the role of FAS in cancer stem cells
  • molecular mechanism of FAS-mediated apoptosis.

Our finding led to discoveries of additional targets in this pathway and provided a strong rationale for using FAS pathway inhibitors for the treatment of both early and late stages of cancer as well as recurrence disease.

Selected publications:

Bandyopadhyay, S., Fulk R.S., Pai, SK., Gross, SC., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Saito, K., Watabe, M., Wang Y., Huggenvik, J. Pauza, ME, Iiizumi, M. and Watabe K. (2005) FAS expression inversely correlates with PTEN level in prostate cancer and an Akt inhibitor synergizes with FAS siRNA to induce apoptosis. Oncogene, 24, 5389

Bandyopadhyay, S., Zhan, R., Wang, Y., Pai, SK., Hirota, S., Hosobe, S., Takano, Y., Saito, K., Furuta, E., Iiizumi, M., Mohinta, S., Watabe, M., Chalfant, C., and Watabe, K. (2006) Mechanism of apoptosis induced by the inhibition of Fatty Acid Synthase in breast cancer cells. Cancer Res. 66, 5934

Furuta, E., Pai, SK., Zhan, R., Bandyopadhyay, S., Watabe, M., Iiizumi, M., Liu, W., Mo, Y-Y., Hirota, S., Hosobe, S.,Tsukada,T., Miura,K., Kamada, S., Saito, K. and Watabe, K. (2008) Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and SREBP. Cancer Res. 68, 1003

Pandey, P.R., Xing, F., Sharma, S., Watabe, M., Pai, S.K., Iiizumi- Gairani, M., Fukuda, K., Hirota, S., Mo, Y.-Y., and Watabe, K. (2012) Elevated lipogenesis in epithelial stem-like cell confers survival advantage in ductal carcinoma in situ of breast cancer. Oncogene, 10, 519