Hedgehog Pathway Cancer and Tumor Regulation

 

Increase Hh Pathway Activation

sdfleads to

up arrowAngiogenic Factors,

Cyclins, anti-apoptotic genes

 down arrowapoptotic genes

 

The hedgehog pathway helps the cancer survive by activating other pathways to help it survive. It turns on pathways that tell the cell to divide, grow new bloods vessels around the tumor (angiogenic factors), and also prevent it for being detected by the immune system.

Angiogenesis

The development of blood vessels is an essential step in the growth of a tumor. Without vessels tumors cannot grow to be larger than a small fraction of an inch. The tumor cells produce (or cause nearby cells to produce) growth factors that stimulate the formation of blood vessels, as shown below.

http://www.cancerquest.org/index.cfm?page=189

 

 

Ref

The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors.

Nat Med. 2001 Jun;7(6):706-11.

Sonic hedgehog inversely regulates the expression of angiopoietin-1 and angiopoietin-2 in fibroblasts.

Int J Mol Med. 2007 Mar;19(3):445-51.

Patched1 functions as a gatekeeper by promoting cell cycle progression.

Cancer Res. 2006 Feb 15;66(4):2081-8.

Role of apoptosis in basal cell and squamous cell carcinoma formation.

Immunol Lett. 2005 Aug 15;100(1):68-72.

Inhibition of smoothened signaling prevents ultraviolet B-induced basal cell carcinomas through regulation of Fas expression and apoptosis.

Cancer Res. 2004 Oct 15;64(20):7545-52.

Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis.

Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5103-8. Epub 2007 Mar 19.