Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.
An open question in Exact Geometric Computation is whether there are transcendental computations that can be made "geometrically exact". Perhaps the simplest such problem in computational geometry is that of computing the shortest obstacle-avoiding path between two points p, q in the plane, where the obstacles are a collection of n discs.This problem can be solved in O(n 2 log n) time in the Real RAM model, but nothing was known about its computability in the standard (Turing) model of computation. We first show the Turing-computability of this problem, provided the radii of the discs are rationally related. We make the usual assumption that the numerical input data are real algebraic numbers. By appealing to effective bounds from transcendental number theory, we further show a single-exponential time upper bound when the input numbers are rational.Our result appears to be the first example of a non-algebraic combinatorial problem which is shown computable. It is also a rare example of transcendental number theory yielding positive computational results.
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