WNT pathway

Barker N, Clevers H (2006) Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov 12 997— 1014... 

Adenomatosis Polyposis Coli (APC). Whereas Dvl is a Wnt pathway activator, GSK3, Axin and APC are all inhibitors. Axin and APC help to stabilize the activity of GSK3, keeping (3-catenin levels low and Wnt target gene transcription off in the absence of a Wnt signal (Fig. 2a). 

Siedensticker MJ, Behrens J (2000) Biochemical interactions in the Wnt pathway. Biochem Biophys Acta 1495 168-182... 

The second group identified 41, which inhibited Wnt pathway activity and proliferation of cancer cells with an aberrant Wnt pathway at micromolar concentrations in contrast, the structurally related analog 42 had no effect. Immobilization of 41 and affinity capture followed by proteo-mics identified several potential targets, including TANK-1 and TANK-2,... 

S. Basu, B. Ellinger, S. Rizzo, C.l. Deraeve, M. Schurmann, H. Preut, H.-D. Arndt, and H. Waldmann, Biology-oriented synthesis of a natural-product inspired oxepane. Collection yields a small-molecule activator of the Wnt-pathway, Proc. Natl. Acad. Sci. USA., 108 (2011) 6805-6810. 

Normally, cell proliferation and cell death are in a steady state, where the rate of proliferation is matched by the rate of apoptosis. Colon cancer, like other cancers, is caused by mutations in key components of regulatory pathways in this case mutations of the tumour-suppressor gene APC, the adenomatous polyposis coli gene. When APC is inactivated and turned off, the Wnt pathway, normally operative only in the embryo, is turned on. The Wnt pathway also plays a role in other cancers, for example in mammary tumours in mice and humans (for further information and literature references, see ref. 14). 

The Wingless-Wnt pathway and p-catenin-APC signalling have much in common. For example, when the Wingless-Wnt pathway is activated in colon cells, the serine/... 

Part 4 considers loss of regulatory control and its consequences with respect to the molecular basis of cancer. It first describes the cellular regulatory proteins that have oncogenic potential, how they can become oncogenic and cause the transformation of normal cells to cancerous cells. Next is an analysis of the loss of developmental controls, the APC protein, (3-catenin, and the Wnt pathway, that lead to mature terminally differentiated cells reverting to immature embryonic cells. The book ends with a summary of the molecular and cellular causes of cancer and an outlook for novel therapies. 

Drugs currently used to treat osteoporosis are classified into those that inhibit osteoclastic bone resorption (including bisphos-phonates, denosumab, and selective estrogen receptor modulators) and those that stimulate bone formation by osteoblasts (parathyroid hormone and derivatives, such as teriparatide). Strontium ranelate may have a dual effect. Other drugs being tested in clinical trials include inhibitors of cathepsin K (an osteoclastic enzyme critical for bone resorption) and of sclerostin (a negative modulator of the Wnt pathway) [21],... 

Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circ Res 109(4) 360-364... 

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