Cancer cells are known to execute reprogramed metabolism of glucose, amino acids, and lipids. Here, we report a significant role of cholesterol metabolism in cancer metastasis. By employing label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of cholesterol esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification.

Abstract-In an open environment such as the Internet, the decision to collaborate with a stranger (e.g., by granting access to a resource) is often based on the characteristics (rather than the identity) of the requester, via digital credentials: Access is granted if Alice's credentials satisfy Bob's access policy. The literature contains many scenarios in which it is desirable to carry out such trust negotiations in a privacy-preserving manner, i.e., so as minimize the disclosure of credentials and/or of access policies. Elegant solutions were proposed for achieving various degrees of privacy-preservation through minimal disclosure. In this paper, we present protocols that protect both sensitive credentials and sensitive policies. That is, Alice gets the resource only if she satisfies the policy, Bob does not learn anything about Alice's credentials (not even whether Alice got access), and Alice learns neither Bob's policy structure nor which credentials caused her to gain access. Our protocols are efficient in terms of communication and in rounds of interaction.

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