The Biochemistry & Cell Biology of Cancer

Cell Biology

What is a characteristic of evading growth suppressors?

1. insensitivity to anti-growth signals

What are characteristics of activating invasion and metastasis?

1. loss of anchorage dependence

2. modification of extracellular matrix components & adhesion

   1. ability to invade adjacent normal tissues and metastasize to distant sites

What are some characteristics of enabling replicative immortality?

1. immortalization in culture by reactivation of telomerase

2. genomic instability

what are some characteristics of inducing angiogenesis?

1. ability to recruit a dedicated blood supply

what are some characteristics of resisting cell death?

1. evasion of programmed cell death (apoptosis)

   1. evading immune destruction

what are some characteristics of sustaining proliferative signaling?

1. loss of cell cycle control

2. growth factor independence

   1. reprogrammed energy metabolism

What is intravasation?

1. getting into the blood vessel via creation of a stimulus

what is extravasation?

leaving an area (not through the same way). for example in coming through a blood vessel one way adn leaving through the other

How is chemotherapy different than targeting the hallmarks of cancer?

Chemotherapy has no specificity; it just kills anything that divides.

What are some pros to targeting the hallmarks of cancer through therapy treatments?

1. healthy cells aren’t being killed, no symptoms are being affected

what is drug efflux mechanism?

it’s when the cancer cells become resistant to chemotherapy

What is senescence?

1. the irreversible cell cycle exit that takes place in either G1 or G2. senescence is also aging, going from G0 to senescence is irreversible, cannot come back to G0

   1. cell cycle arrest is mediated by p16/p21 dependent CDK inactivation, containing high levels of G1 cyclins (cyclin D and E) associated with inactive CDK.

What is quiescence?

1. G0

2. the reversible cell cycle exit that occurs in G1 prior to the restriction point.

   1. it’s mediated by p27-dependent CDK inactivation and cyclin D1 downregulatio

What is checked at the G2 checkpoint?

proper chromosome duplication

what is checked at the M checkpoint?

attachment of each kinetochore to a spindle fiber

what is assessed at the G1 checkpoint?

the integrity of the DNA

What regulates the whole cell cycle?

checkpoint kinases

What controls Chk2?

ATM

What controls Chk1?

ATR

Name some negative regulators or the cell cycle

Retinoblastoma (Rb), p53, p21

What happens if Rb isn’t phosphorylated?

it binds to E2F, preventing it from binding to DNA and initiating transcription

What happens if Rb is phosphorylated?

there’s a conformational change so E2F can go and act on the DNA

is Rb phosphorylation good for cancer progression?

no, as that means phosphorylation can lead to E2F initiating transcription

What happens when a tumor suppressor like p53 gets mutated?

p53 programs for controlled cell death, so in the case the cell cycle would continue and the cells can become cancerous

What phase is cyclin E peak at?

between G1 and S phase

What phase is cyclin A peak at?

between s phase and g2 phase

What phase does cyclin B peak at?

between G2 and mitosis

What are CDKs?

protein kinases that, when fully activated, can phosphorylate and activate other proteins that advance the cell cycle past a checkpoint

how does CDK become fully activated?

1. CDK binds to cyclin so it can be phosphorylated by another kinase.

   1. if not bound together kinase doesn’t happen (induced fit)

what are proto-oncogenes?

1. genes that code for positive cell cycle regulators.

   1. these are normal genes that when mutated in certain ways become oncogenes; genes that cause a cell to become cancerous

which steps of the cell cycle are monitored by checkpoints?

1. near the end of G1

2. G2/M transition

3. during metaphase

what are stem cells?

they are cells that have unlimited self-renewal capacity. they divide into two types of daughter cells, one that replicates and one that differentiates

in the case of cancer, what happens to your stem cells?

they increase

what is a totipotent cell?

a cell that’s capable of forming any cell type like a complete embryo

what is a multipotent stem cell?

a cell that’s capable of forming a limited number of cell fates or closely related families of cells

what is a pluripotent cell?

a cell capable of forming several different cell types but more limited than multipotent cells

what is a unipotent stem cell?

a stem cell only capable of forming only one type of cell

what happens to proliferation and differentiation in cancer cells

Differentiation of cells leads to dying cells, it also leads to degenerative disease. proliferation is in cancer cells

what type of cells can restricted progenitor cells give rise to?

mature cells

what does clonal mean?

originates from a single cell

briefly explain the cancer stem cell hypothesis

cancer, the entity, is surrounded by non-tumorigenic entities so it’ll die quickly. imagine cancer is a little ball in the middle surrounded/hiding by a bunch of other non cancer balls.

“signal transduction (signaling) can be ______ or _______

tumor promoting or tumor suppressing

what is the reductionist view of cancer?

cancer is made up of one type of cell. this isn’t true as cancer itself is made up of a combination of many different types of cell. note that cancer needs other cells to get energy, especially blood vessels

how can invasive cancer move?

it becomes more spindle shaped

what triggers angiogenesis?

VEGF: Vascular Endothelial Growth Factor

what is parenchyma?

the most predominant cell in the organ, every organ is made up of many different types of cells