Robbins chapitre 7

Question 1

What does MMP does, on top of remodeling basal membrane and interstitial tissue?

Answer 1

releasing factors that contribute to malignancy of cancer: ex: stimulate the release of VEGF from ECM

Question 2

what is anoikis?

Answer 2

'’without home’’ = lack of adhesion in cancer cells

Question 3

Why do some metastasis have tropism for certain organs?

Answer 3

1. they express adhesion molecules whose ligands are found preferentially on the endothelial cells of target organ.
   ex: CD44-> lymphoid organs
2. they have chemokine receptors
3. '’favorable soil’’

Question 4

what is tumor dormancy

Answer 4

when metastasis happen and cell survive bt fail to grow

Question 5

Which is the most reliable factor to dertermine malignancy, outside of metastases?

Answer 5

invasiveness

Question 6

lymphatic spread of cancer is typical of which tumor? hematogenous?

Answer 6

carcinoma

sarcoma

Question 7

why does chronic inflammation increase risk of cancer?

Answer 7

increased stem cells in tissues

reactive oxygen species dammaging dna

inflammatory mediator that promote cell survival even if genomic dammage

increased cellular replication

Question 8

3 acquired conditions that increase risk of cancer

Answer 8

chronic inflammation, precursor lesion, immunodeficiency

Question 9

In cancer, why does mutations that interfere with host immune responses or altering interaction with stroma, etc, aren’t classified as driver or passenger mutation?

Answer 9

because passenger/driver is restricted to genes influencing the behavior of the cells in a cell-intrinsic manner

Question 10

what is the role that wirtually all oncoproteins have?

Answer 10

encode active oncoproteins that participate in signaling pathways that drive the proliferation of cells

Question 11

Which is the most common protooncogen affected in cancer?

Answer 11

MYC

Question 12

Name a few things the protooncogene can do when mutated

Answer 12

activate expression of many genes involved in cell growth (D cyclins, upregulae rRNA and rRNA processing, Warburg effect), upregulate expression of telomerase, reprogram somatic cells into pluripotent stem cells

Question 13

which is more important in cancer: defect in G1/S or G2/M?

Answer 13

G1S bc create a mutator phenotype (lack of DNA repair)

Question 14

which are the 2 major mutations associated with cancer that affect the G1/S checkpoint of the cell cycle?

Answer 14

Gain of function mutation in D cyclin genes and CDK4 (promote unregulated G1/S progression)

Loss of function mutations in genes that inhibit G1/S progression
ex: P16

Question 15

What do RB and p53 do in the cell cycle?

Answer 15

they are tumor supressors

RB: role at G1/S

Question 16

Name the 4 main key regulators of the cell cycle, almost always involved in cancer

Answer 16

P16/INK4a, cyclin D, CDK4, RB (or upstream factors)

Question 17

RB stop the cell cycle when it is hyperphosphorylated or hypophosphorylated?

Answer 17

hypophosphorylated

Question 18

when in the cell cycle does P53 cause arrest?

Answer 18

late G1

Question 19

What is senescence?

Answer 19

permanent cell cysle arrest

Question 20

E-cadehrin/b-catenin are frequent mutations in which tumors?

Answer 20

carcinoma

Question 21

What does a mutation of isocitrate dehydrogenase do ?

Answer 21

it is a Krebs cycle enzyme. It gives the oncometabolite 2-hydroxyglutarate, which is a oncomeabolite, which cause epigenetic changes of cells, causing cancer

Question 22

which are the 2 major mecanisms by which apoptosis is avoided by cancer cells ? (intrinsinc pathway of apoptosis)

Answer 22

loss of TP53 (prevent the upregulation of PUMA, a proapoptotic BH3 only protein

Overexpression of the BCL2 family (antiapoptotic)

Question 24

One of the ways tumors evade the immune sysem is by no expressing MHC (fail to express normal levels of HLA class 1 molecules). However, this may trigger which immune cell?

Answer 24

NK

Question 25

A way for tumors to evade the immune system is the upregulate negative regulatory chekpoints tha suppress immune response (ex: promote the expression of the inhibitory receptor _______ on tumor specific T cells)

Answer 25

CTLA-4

Question 26

which cytokine is frequently secreted by tumors?

Answer 26

TGF-beta

other: IL10, prostaglandin E2, VEGF, etc

Question 27

Which ype of T cells does tumors favor the developpment to evade the immune system?

Answer 27

Treg

Question 28

What is chromohrypsis (chromosome rearrangement in cancer)

Answer 28

dozens to hundreds of chromosome breaks in one or multiple chromosome.

Question 29

direct vs indirect acting carcinogen

Answer 29

indirect= requires metabolic conversion to become active carcinogens (ultimate carcinogens)