1. Growth Factors, Receptors,
Chapter 5:
Growth Factors, Receptors,
and Cancer

2. Spatial and temporal control of cell growth and differentiation via communication between individual cells are pivotal for maintaining functional and structural integrity of tissues and organs

3. e.g. Wound healing

4. Effect of growth factors on cell proliferation and migration

5. Experimental clues for cell-to-cell signaling via growth factors from studies for the tyrosine kinase activity of v-Src

6. Pleiotropic actions and substrate specificity of protein kinases

7. [1] Receptor tyrosine kinases (RTKs)

8. Structures of RTKs

10. Alterations in structures and expression of RTKs make them function as oncogenes

14. Human A431 epidermoid carcinoma cells
Transphosphorylation underlies the operation of RTKs
Human A431 epidermoid carcinoma cells

15. 206 human glioblastomas

16. Alternative mechanisms of growth factor-induced receptor dimerization

17. Constitutive dimerization of RTKs by gene fusion

19. Multiple structural alteration affecting Kit firing

20. [2] Cytokine receptor noncovalently interacting with tyrosine kinases

21. [3] Receptors with serine/threonine kinase activity

22. [4] Notch receptor of which activation depends on proteolytic cleavage

23. [5] Patched-smoothened signaling system (Hedgehog pathway)

24. [6] Canonical Wnt signaling via frizzled receptors

25. [6] Non-canonical Wnt signaling via frizzled receptors:
G-protein-coupled receptor (GPCR)

26. [7] Nuclear receptors activated by lipophilic ligands

27. [8] Receptors sensing association between the cell and the extracellular matrix (ECM)

29. Integrins

31. Integrin tethering to the ECM and cytoskeleton

32. Suppressed mammary tumorigenesis in the absence of b1 integrin

33. Activation of Ras, a small-GTP binding protein, by RTKs

34. EGFR*
Grb2
SOS
Ras*
Raf*
MEK
ERK1/2
RSK
Myc
Elk-1
Translation
Transcription
EGFR mutaion:
 NSCLC (10%)
 Glioblastoma (20%)
EGFR overexpression:
 Colorectal cancer (22-77%)
 Pancreatic cancer (30-50%)
 Lung cancer (40-80%)
 Non-small cell lung cancer (14-91%)
Ras mutation:
 Papillary thyroid cancer (90%)
 Pancreatic cancer (60%)
 Colon cancer (50%)
 Non-small cell lung cancer (30%)
B-raf mutation:
 Melanoma (70%)
 Papillary thyroid cancer (50%)
 Colon cancer (10%)
Survival / Proliferation / Suppression of apoptosis
Imatinib
Farnesyl
transferase
SB590885
PLX4720
XL281
RAF256
Sorafenib
PLX4032
XL518
CI-1040
PD035091
AZD6244
GSK
Ras/Raf/MAPK signaling cascade activated in human cancers and anti-cancer drugs, targeting the pathway, currently in development. Asterisk indicates mutations found in human cancers.

36. Alternative mechanisms of transformation by Ras