Books for lectures / !!! SignMolecDiffProlif Pictures

Vasculogenesis and Angiogenesis

Vasculogenesis involves formation of initial blood islands and construction of capillary networks

Angiogenesis involves formation of new blood vessels.

Nitric Oxide (NO) signaling

NO can act as a diffusible messenger

Intracellular Receptors

●Steroid/Thyroid hormone super-familyily ofof receptors

●contain ligand and DNA binding domains

●reside in cytoplasm, bind ligand thenn migrate to nucleus where they interactact with specific DNA sequences

Steroid

Hormone

Receptors

APC in GI Cancers

!FAP due to germline mutations in APCPC

!Somatic (sporadic) mutations in the APC gene initiate colorectal malignancyancy

!APC mutations in 63% of colonic adenomas

!99% of germline and 100% of sporadicadic APC mutations lead to truncated proteinotein

Significance of Signal Transduction to Disease::

Tumorigenesis

●Cancer cells contain genetic damage

●many of the genes encoding signaling molecules have been shown to be capablele ofof causing cancer if disrupted in some way

APC Function

!APC associates with β -catenin, a proteinn involved in the Wnt signaling pathway

!APC induces β -catenin phos. leading to itsits degradation

!β -catenin acts as transcription factor, inducesuces genes like MYC

!β -catenin also linked to intercellular adhesionesion molecules, e.g. E-cadherin

Wnt signalingaling

β -catenin bound in complex which includes GSK-3; this kinase phosphorylates β - catenin leading to its degradation.

Activation of disheveled causes inhibition of GSK-3. β -catenin builds up, is released from complex, and translocates to nucleus where it forms part of a transcription factor complex to activate gene expression