Figure 3: Cell Signaling. Cells communicate with
each other through a variety of methods, including
hormones, growth factors, elements like calcium,
and gases like nitric oxide. These signals originate
within a given cell, leave that cell, find, enter, and
are interpreted by a different cell. This process of
communication is called cell signaling and is
Each type of signal (growth factor, calcium,
hormone, etc.) has a specific receiving protein,
called a receptor, and its own network of other
proteins (blue blobs) that aid in the processing of
that particular signal. These individual networks
are often referred to as pathways. Many networks
can interface with other networks, impacting how
different signals are interpreted and providing an
integrated signal to the cell. Often, signals are
relayed from the receiving protein across the
network and into the nucleus of the cell (N), where
changes in gene activity (red strands) and
ultimately cell behavior occur as a result.
Figure 2: The Cell Cycle. The cell cycle functions like a computer to govern the process leading to cell division, processing a multitude of inputs
from both inside and outside of the cell and synthesizing that into one of two choices for the cell: proliferate or settle down, also known as
quiescence. Within the quiescent state, also known as Gap 0 or G0 (G0 circle), there exist at least two options: remain quiescent, but capable of
re-entering the cell cycle (arrows to/from G0 to G1); or terminally differentiate into a more specialized cell that can no longer re-enter the cell
cycle, called post-mitotic.
The various inputs that are processed by the cell cycle include, but are not limited to: the energy state of the cell (G), including nutrient and
oxygen levels; the presence of stimulatory growth factors (I); and the status of the microenvironment (H). The balance of these factors ultimately
determines if a cell will enter the cell cycle to make more copies of itself or enter the quiescent state.
The cell is only sensitive to these inputs during a particular period within the Gap 1, or G1 phase (G1 arrow), of the cell cycle (red portion of G1
arrow), leading up to a major checkpoint called the restriction point (R), which maintains the fidelity of the cell cycle. Prior to the restriction
point, the cell can transit between quiescence and the cell cycle; however, once the restriction point is passed, the cell cycle will proceed and
the cell will divide, making new cells.
The actual work performed during the cell cycle is done by a large family of proteins called cyclin-dependent kinases (cdks), which are controlled
by a number of inputs including a family of cyclin-dependent kinase inhibitors (not shown). These enzymes are in turn regulated by a central
controller, the tumor suppressor known as the retinoblastoma protein or Rb. The activity of Rb controls transit through the restriction point, and
Rb must be inactivated in order for the cell cycle to progress. Many oncoproteins, including those of viral origin like HPV’s E7, inactivate Rb,
which is inactivated in many cancers, allowing for uncontrolled progression of the cell cycle.
In addition to the restriction point, the cell cycle contains at least four main checkpoints (stoplights), which function to ensure that the previous
phase of the cell cycle was completed without errors prior to moving to the next phase. Therefore, these checkpoints can also function as tumor
suppressors. During S phase (S arrow), families of proteins known as DNA damage response proteins inspect the newly copied DNA for errors,
and repair enzymes correct any found. These errors can come from the process of DNA replication itself or from various chemicals, radiation or
other DNA toxins. DNA damage responders like BRCA1 and 2, the RAD family of proteins, and others are often non-functional in many cancers,
allowing the cell cycle to proceed despite errors in the DNA. As these errors accumulate within a precancerous cell, they often confer a competitive
advantage to the cell allowing it to operate and multiply independently of the checkpoints in the cell cycle, ultimately leading to cancer.
Cell division itself occurs by a process called mitosis, (M phase; see M arrow), which is a coordinated effort between the DNA (blue), the organelles
of the cell, and the cell cytoskeleton (green). Mitosis consists of several steps: prophase, metaphase, anaphase, and telophase; the period
between cell divisions is known as interphase. During prophase (A), the DNA condenses forming chromosomes visible under the microscope.
These chromosomes then attach to the cytoskeleton and begin to align in the center of the cell during prometaphase (B) and are completely
aligned during metaphase (C). The cytoskeleton then moves the two copies of each chromosome, formed during the S phase replication process,
towards opposite ends of the cell during anaphase (D). Once the chromosomes have arrived at opposite ends, the remaining contents of the cell
are divided and new cell membranes and cytoskeletons are formed during telophase (E). During the process of cytokinesis (E and F), the dividing
cell pinches apart into two daughter cells (F).