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