Robbins chapitre 7 Flashcards
What does MMP does, on top of remodeling basal membrane and interstitial tissue?
releasing factors that contribute to malignancy of cancer: ex: stimulate the release of VEGF from ECM
what is anoikis?
'’without home’’ = lack of adhesion in cancer cells
Why do some metastasis have tropism for certain organs?
- they express adhesion molecules whose ligands are found preferentially on the endothelial cells of target organ.
ex: CD44-> lymphoid organs - they have chemokine receptors
- '’favorable soil’’
what is tumor dormancy
when metastasis happen and cell survive bt fail to grow
Which is the most reliable factor to dertermine malignancy, outside of metastases?
invasiveness
lymphatic spread of cancer is typical of which tumor? hematogenous?
carcinoma
sarcoma
why does chronic inflammation increase risk of cancer?
increased stem cells in tissues
reactive oxygen species dammaging dna
inflammatory mediator that promote cell survival even if genomic dammage
increased cellular replication
3 acquired conditions that increase risk of cancer
chronic inflammation, precursor lesion, immunodeficiency
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?
because passenger/driver is restricted to genes influencing the behavior of the cells in a cell-intrinsic manner
what is the role that wirtually all oncoproteins have?
encode active oncoproteins that participate in signaling pathways that drive the proliferation of cells
Which is the most common protooncogen affected in cancer?
MYC
Name a few things the protooncogene can do when mutated
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
which is more important in cancer: defect in G1/S or G2/M?
G1S bc create a mutator phenotype (lack of DNA repair)
which are the 2 major mutations associated with cancer that affect the G1/S checkpoint of the cell cycle?
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
What do RB and p53 do in the cell cycle?
they are tumor supressors
RB: role at G1/S
Name the 4 main key regulators of the cell cycle, almost always involved in cancer
P16/INK4a, cyclin D, CDK4, RB (or upstream factors)
RB stop the cell cycle when it is hyperphosphorylated or hypophosphorylated?
hypophosphorylated
when in the cell cycle does P53 cause arrest?
late G1
What is senescence?
permanent cell cysle arrest
E-cadehrin/b-catenin are frequent mutations in which tumors?
carcinoma
What does a mutation of isocitrate dehydrogenase do ?
it is a Krebs cycle enzyme. It gives the oncometabolite 2-hydroxyglutarate, which is a oncomeabolite, which cause epigenetic changes of cells, causing cancer
which are the 2 major mecanisms by which apoptosis is avoided by cancer cells ? (intrinsinc pathway of apoptosis)
loss of TP53 (prevent the upregulation of PUMA, a proapoptotic BH3 only protein
Overexpression of the BCL2 family (antiapoptotic)
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?
NK
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)
CTLA-4
which cytokine is frequently secreted by tumors?
TGF-beta
other: IL10, prostaglandin E2, VEGF, etc
Which ype of T cells does tumors favor the developpment to evade the immune system?
Treg
What is chromohrypsis (chromosome rearrangement in cancer)
dozens to hundreds of chromosome breaks in one or multiple chromosome.
direct vs indirect acting carcinogen
indirect= requires metabolic conversion to become active carcinogens (ultimate carcinogens)
Which are the cytokines that have a role in cachexia in cancer? (3)
IL6 TNF, IL1
