Cancer Biology

1. The Hallmarks of Cancer
Karobi Moitra (Ph.D)
NCI Frederick , NIH
Cancer Inflammation Program
Human Genetics Section
Frederick MD.

2. Acquired
Capabilities
of Cancer
Cells

4. 1. Self-Sufficiency in growth signals
Normal cells require mitogenic (cell div) growth signals to
move from a quiescent (resting) state into an active
proliferation state. Cancer cells can generate their own
growth signals.

5. Autocrine signaling : Secretion of a substance or growth
factor that acts on a cell that produced it (i.e. IL2 signaling
in monocytes )
Paracrine signaling: secretion of a substance or growth
that acts on a nearby cell (i.e. neurotransmitter signaling)
Autocrine

6. How do cancer cells generate their own growth signals ?
Autocrine signaling: a cancer cell can manufacture it’s
own autocrine growth factors.
Active transforming growth factor beta blocks proliferation in normal cell, while downregulation of TGF-beta
in a cancer cell can induce proliferation by upregulation of cyclins and autocrine growth factors
(hypothetical example Grimm and Rosen 2006).

7. Cancer cells can also switch the types of
Extracellular matrix receptors (ECM) they express favoring the
ones that transmit growth signals
ECM : extracellular part of tissue that provides structural
support to the cells and performs various other functions

8. GRB2- growth factor
receptor bound protein
Growth signals
MEK - mitogen activated
protein kinase kinase
ERK -
Extracellular signal
regulated kinase
Activation of the Ras-raf pathway through integrins
(integrins can mediate signals from the ECM to the
cell)

10. 2. Insensitivity to Antigrowth signals
If cancer cells are to survive they must block anti-growth
signals. Antigrowth signals can block proliferation by
a. Forcing a cell out of the cell cycle into G0.
b. Inducing a cell to enter post-mitotic differentiated
state.

11. Transcription factors: switch genes on

12. E2F is a transcription factor which can switch on genes
that can cause cell division. Rb can inactivate E2F.

13. Loss of pRB tumor suppressor

15. 3. Evading Apoptosis (cell suicide)

16. Mutations in p53 can derail apoptosis (prevent
cell suicide)

17. What happens when there is a ‘mistake’ or mutation in the code?

18. Mutations in p53 can derail apoptosis

19. Insulin like Growth Factors (IGFs) trigger pro-survival
(anti-apoptotic) pathways

21. 4. Limitless Replicative Potential
Telomere
Normal cells age by shortening of chromosomes when
their telomeres degrade

22. Telomerase synthesizes and maintains telomeres
in cancer cells

24. 5. Sustained Angiogenesis
Angiogenesis is the growth of new blood vessels

25. VEGF - Vascular endothelial growth factor and
angiogenesis

26. The VEGF pathway

28. 6. Tissue invasion and metastasis

29. Cancer cells synthesize collagenase type lV

30. E-cadherin is disregulated in invasion and metastasis
Loss of anchorage dependence
E- Cadherin

31. Parallel
Pathways
Of
Tumorigenesis

32. Reference: The Hallmarks of Cancer , Hanahan D and Weinberg R (2000)
Cell, 100: 57-70.