Final Exam (new) Flashcards
characteristics of cancer cells
no contact inhibition of growth low growth factor requirements no anchorage dependence no cell cycle checkpoints abnormal karyotypic profile indefinite life span
what does lack of contact inhibition mean?
cancer cells do not stop dividing when they are in contact with other cells, results in cancer cells growing on top of each other
what does it mean that cancer cells are anchorage independent?
they do not attach to the substrate and appear rounded instead of spread out like normal cells
how do tumors stimulate angiogenesis?
they secrete VEGF which stimulates formation of new blood vessels (angiogenesis) and promotes survival/growth
what’s the Warburg effect?
cancer cells may switch from mostly using oxidative phosphorylation to using mostly glycolysis. this results in available carbon atoms (building blocks from incompletely oxidized glucose) to be used for synthesis of proteins, nucleic acids, and lipids needed for growth
how do cancer cells exhibit genetic instability?
DNA replication and repair are more prone to error and mutations. DNA repair proteins are mutated and overall mutation rate increases
philadelphia chromosome
an altered chromosome 22 used as identifier of leukemia. translocation means Ber gene fuses with Abl and results in constitutively active signaling pathway leading to increased cell survival, growth, and proliferation
cancer cells are defined by excessive proliferation and invasion of other tissues. how does this explain benign and malignant tumors?
when cells do not have the invasiveness property they are benign. Once a tumor spreads to other cells and invades tissues it become malignant.
metastases are
secondary tumors created when a primary tumor cell migrates to another tissue and invades. stages of metastasis vary in difficulty such that escaping parent tissue is difficult but travel through circulation is easy, then colonization of the new site is difficult
what is intravasation and extravasation?
tumor cells leave the primary tumor and enter the vascular system by intravasation. tumor cells establish secondary tumors in other tissues through extravasation and invasion
what percent of the human genome is cancer-critical?
1%
two classes of cancer-critical genes
oncogenes: encode proteins having gain-of-function mutations, leads to overactive genes
tumor suppressor genes: encode proteins that normally prevent excessive cell survival and proliferation
how many copies of mutation are needed to cause cancer in the two types of cancer-critical genes?
oncogenes: proto-oncogenes only need one mutated copy of gene to become overactive oncogenes
tumor suppressor genes: both copies must be mutated to lose tumor prevention functionality
how can the Wnt signaling pathway lead to colorectal cancer?
APC protein keeps the Wnt signaling pathway inactive in absence of Wnt protein. APC causes degradation of beta-catenin which prevents activation of gene transcription.
mutation of APC leads to accumulation of beta-catenin and drives transcription, leading to proliferation of stem cells and potentially cancer
how many mutations are needed in the same cell before tumor state is reached?
4-6 different mutations
three common pathways that are disrupted and cause cancer
- RTK/Ras/PI3K pathway
- Rb pathway
- p53 pathway
RTK/Ras/PI3K pathway mutations
pathway is normally activated by 2 signals, in cancer cells the pathway is activated without signals. leads to hyperactive Was that increases transcription and movement through cell cycle
Rb pathway mutations
retinoblastoma protein (pRb) is a universal regulator of the cell cycle. it binds to transcription factor E2F and inactivates it, stopping cell division. mutation causes abnormal cell proliferation. the transcription factor Myc can cause hyperactive pRb if it is constitutively active
p53 pathway mutations
p53 is activated at the G1/S transition where DNA integrity is checked before S phase. p53 stops damaged DNA from replicating, and so is called guardian angel gene. p53 is stabilized by phosphorylation which makes sure it only works when it should
why does chance of getting cancer skyrocket with age?
it takes time to accumulate numerous mutations in the same cells
how can obesity lead to cancer?
fat cells make extra hormones and growth factors which tell cells to divide more often. this increases the chance of cancer cells being produced
2 cancer vaccines
human papillomavirus (HPV): STD that causes cervical cancer by sequestering p53 and pRb proteins, enabling uncontrolled cell proliferation. vaccines protect women from cervical cancer Hepatisis B (HBV)
cancer treatment pathways
exploit genetic instability and loss of cell-cycle checkpoint responses in cancer cells
drugs kill cancer cells selectively by targeting specific mutations
small molecules can inhibit specific oncogenic proteins
enhancing immune response against specific tumor
Tasmanian devil cancer transmitted how?
transmitted through biting
why do elephants have low cancer incidence?
they have extra copies of genes like p53 and leukemia inhibitory factor 6
what is the extracellular matrix?
an intricate network of macromolecules essential for support/scaffolding of cells
pericellular vs interstitial matrix
pericellular: just beyond the PM, lies between PM and interstitial matrix
interstitial: lies further away from PM
functions of ECM
support structure, allows for anchorage
controls communication between cells
regulates cell growth, migration, differentiation
segregates tissues
provides place for active exchange of metabolites, ion, water
what makes up the ECM
glycosaminoglycans/ proteoglycans
fibrous proteins (collagen)
glycoproteins (fibronectin, laminin)
what are GAGs? important parts of their structure?
glycosaminoglycans are unbranched polysaccharide chains and have sulfate and carboxyl groups (negative charged). they are still and don’t fold. the charge and stiffness give ECM gel-like substance.
hyaluronan
no sulfated sugars. produced directly from cell surface. plays roles in development (heart valve), wound healing, and joint fluid
only GAG that doesn’t have a GAG chain covalently linked to a core protein
proteoglycans
GAG chains linked to a core protein, includes all GAGs except Hyaluronan.
aggrecans
aggregations of proteoglycans in to large structures
collagen structure
triple helix
how much of total protein mass is attributed to collagen?
25%
purpose of fibril associated collagens
help organize fibrils and allow for collagen fibrils to resist tensile forces
fibronectin
a large glycoprotein found in all vertebrates. it’s a dimer joined by disulfide bonds. has an RGD sequence that serves as sites for cell surface binding (Integrins)
how many polypeptide chains are present in a laminin? what does laminin do?
3 held together by disulfide bonds
laminin is the primary organizer of the orderly sheet structure of basal lamina
basal lamina
specialized form of ECM with laminin and type IV collagen as major components. its thin, tough, flexible, and adds support.
integrins
transmembrane heterodimers that link the ECM to the cytoskeleton. they switch between inactive and active to allow for cell crawling. talin and vinsulin are involved in cytoplasmic complex that attaches to the cytoskeleton.
connects directly to fibronectin and indirectly to actin
hemidesmosomes
epithelial cell-matrix junctions where Integrins attach to keratin intermediate filaments instead of actin
why do Integrins cluster?
increases cell adhesion ability
Integrins also control
survival, growth, and proliferation through signaling by ECM
cadherins
adhesion proteins for cell-cell anchoring junctions. they are dependent on other molecules binding to them to stabilize them. Ca2+ prevents flexing
what does it mean that cadherins are symmetrical and homophilic in their binding?
cadherins on one cell will bind to the same type of cadherin on the other cell. the bonds are weak, but may parallel bonds adds strength
how do cadherins guide organization in developing organisms?
homophilic binding means that cells of similar types will stick together and congregate in the right area
linkage of classic cadherins to cytoskeleton requires what?
adaptor proteins, including catenins. these allow for dynamic sensing that regulate behavior in response to changing mechanical conditions. alpha-catenin uncovers vinculin binding site and recruits actin, causing g shape change
adhesion belts
junctions can link contractile cells and coordinate actin cytoskeletons, important for animal development
desmosomes
similar to adherins, differ in type of cadherin present and link to intermediate filaments instead of actin. gives epithelia mechanical strength
tight junctions
form a seal between cells and a fence between PM domains. contain strands of adhesion proteins like Claudin (essential for formation), Occludin (limits permeability), and tricellulin.
gap junctions
form a continuous aqueous channel that connect cell interiors (cells are electrically and metabolically coupled). gap junctions can flip between open and closed states
what makes up gap junctions?
6 connexin subunits make a connexon. they can be combined differently to be homo/heteromeric and homo/heterotypic in different tissues for different properties
plasmodesmata
used in plants to perform similar function to gap junctions
selectins
(specialized adhesion mechanism) mediates transient (weak) cell-cell adhesions to allow for white blood cels to roll to area of inflammation. then strong adhesion allows for extravasation
