Cancer Biology Notes PDF

CANCER BIOLOGY Term Definition Purpose/ Examples CANCER CELLS Cancer A (genetic, among other things) disease caused by...

CANCER BIOLOGY Term Definition Purpose/ Examples CANCER CELLS Cancer A (genetic, among other things) disease caused by an uncontrolled division of abnormal cells in a part of the body -​ tend to produce death or deterioration -​ Tend to infiltrate, metastasize, and terminate a malignant tumour fatally (malignant malaria) Cancer cells behave in this abnormal manner because of changes in the DNA sequence of key genes, which are known as cancer genes The only way to confirm uncontrolled division is a biopsy (remove a sample of tissue or tumour from the body for examination under a microscope) -​ KI 67: marker of cell division -​ Malignant malaria tending to infiltrate, metastasize, and terminate a malignant tumour fatally -​ Hallmarks of 1.​ Self-sufficiency in growth signals Cancer 2.​ Insensitivity to antigrowth signals 3.​ Evading apoptosis 4.​ Limitless replicative potential 5.​ Sustained angiogenesis (formation of new blood vessels) 6.​ Tissue invasion and metastasis GAARAM Gotta anticipate ants roaming around me Cancer cells -​ Arise from single cells -​ Have altered genomes -​ Cancer cells lose their contact inhibition -​ usually clonal in origin (X-inactivation clones replicated)  -​ Rudolf Virchow, -​ 1858 -​ All cells arise from single, other cells -​ Metastatic cancer cells resemble the primary cells -​ every cell within a tumour is equally likely to be the cell of origin -​ Contact Inhibition cell's ability to cease proliferation and growth when they contact each other keeps them from forming into a layer Cancerous cells typically lose this property and divide and grow over each other uncontrolled even when in contact with neighbouring cells. Results in the invasion of surrounding tissues, their metastasis to nearby organs, and eventually tumours -​ Normal vs. Cancer Cells Normal Cancer Cytokines Missing Cytokines Large cytoplasm Small Cytoplasm Single Nucleus Multiple nuclei Single nucleolus Multiple and large nucleolus Fine Chromatin Coarse chromatin Contact Inhibition No Contact Inhibition Tumour Cell biological - Substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine markers -​ Hormones (Epi – in blood, adrenal medullary tumour) -​ Enzymes -​ Genes -​ Antigens (PSA – in blood, prostate cancer) -​ Antibodies HEGAA Huge epic gigantic ant asses  - There is no necrotic core in stage one cancers, so it is a biomarker -​ The necrotic core is dead and very acidic and is found within the center of the tumour. -​ The living tissue that will become a tumour is the outside ring. -​ It has a different antigen and the pH of the native environment. -​ Selection for Cells must make critical decisions to survive in a multi-cellular organism Single-Cell -​ Stem cell renewal Survival -​ Differentiation -​ Growth /quiescence -​ Death SDGD Sweet dog great dog Things can go wrong at all these levels NEOPLASMS Diagnosis of Neoplasms Symptoms: -​ Weight loss, Rectal Bleeding, Persistent cough Screening: -​ Pap smear, Mammogram, Occult blood Incidental: -​ Radiology (~1gm/10^9 cells) Treatment: 1.​ Biopsy 2.​ Histopathology (autopsy) 3.​ Staging (autopsy) -​ Anaplasia lack of differentiation (loss of specificity to functions) Anaplasia = anesthesia = you forget whats going on -​ Neoplasia Any abnormal new growth -​ Hyperplasia increased NUMBER of cells in one area -​ Hypertrophy increased SIZE of cells -​ Dysplasia disorderly proliferation of cells (cells multiply and change form) Not cancerous yet -​ In Situ (in original Cancer-looking cells are found only in the place where place) Cancer they first formed and haven't spread to nearby tissue. At some point, these cells may become cancerous and spread into nearby normal tissue. -​ Benign Tumor Not cancer tumour cells grow only locally and cannot spread by invasion or metastasis Malignant Tumor Cancer cells invade neighbouring tissues, enter blood vessels and metastasize -​ Linear tumour one dominant clone giving rise to others development metastatic clones arise as a late result of the evolution of the primary tumour -​ Parallel tumour multiple groups of cancer cells arise at the same time, development all with different mutations/jobs early disseminating clones escaping the primary tumour, evolving separately, and forming late metastases Lose clonal identity with each stage Non-white → treatment-resistant. -​ Clonal selection One change from identical cells becomes a tumour one cell with a feature gets selected and copied over and over. Doesn't affectthe existing cell population -​ Clonal dominance One cell overtakes the existing cell population and becomes a tumour when a trait of a cell is replicated enough it is the dominant cell/trait. Cancer Stem Cell (usually developmental cancer) is different than a Stem Cell Invasion Steps of tumour invasion: 1.​ Cellular multiplication -​ By altering mitotic rate vs. cellular death rate ratios 2.​ Mechanical pressure 3.​ Release of lytic enzymes 4.​ Decreased cell-to-cell adhesion 5.​ Increased motility -​ intravasation (entry of cancer cells into the blood vessels) and extravasation (exit of cancer cells from the blood vessels to invade secondary organs) MMLAM My mom loves ants much -​ Three-step Theory 1. Tumour cell attachment of Invasion -​ Fibronectin and laminin as proteins 2. Degradation of matrix -​ Using enzymes 3. Locomotion into the matrix -​ Using Invadopodia (which are pseudopodia) -​ Invadopodia degrade extracellular matrix so that cells can enter into new environments ADL Ants die last Benign colonic Proliferative abnormality: abnormal secretion by the neoplasms plasma cells -​ Tubular adenoma precancerous polyps only about 10% become cancerous -​ villous adenoma growth patterns are more likely to have cancer cells in them (15-25% become cancerous) -​ Hyperplastic small, located in the end portion of the colon (the polyps rectum and sigmoid colon) have no potential to become malignant -​ Dysplastic polyps Colon cells look very abnormal and more like cancer cells -​ Clinical Features Most likely to occur on the right side, in elderly women over sixty, with a unique metastatic pattern TMN SYSTEM 1.​ CIS (Stage 0) Carcinoma in situ “Pre-cancer” Glandular or epithelial lesions no potential for metastasis unless it progresses into cancer 2.​ Stage 1 Confined to the organ of origin, contained (colonially pure) 3.​ Stage 2 Locally invasive (nearby tissue) 4.​ Stage 3 Spread to lymph nodes 5.​ Stage 4 Spread to distant sites (different types of cells) CIS → Organ → Nearby tissue → Lymph nodes → Distant Sites Essential TNM A registry tool to reduce gaps in cancer staging Information -​ M - Metastasis M-0: Tested nodes are cancer-free M-1: Tested nodes show cancer cells or micrometastasis -​ T - Tumor size T-1: 0-2 cm T-2: 2-5 cm T-3: >5 cm (invasion into the lower third of the vagina, invasion to pelvic side wall) T-4: Tumor has broken through the skin or attached to chest wall (invasion into the rectum or bladder) -​ N - Lymph node N-0: Surgeons can't feel any nodes status N-1: Surgeon can feel swollen nodes N-2: Nodes feel swollen and lumpy N-3: Swollen nodes located near collarbone MUTATION 1.​ Oncogenes Formation of cancer -​ Mutations in cancer genes can occur somatically or can be inherited. -​ Increases in mutation rate or genomic instability increase the frequency of cancer. Are cancerous when active 2.​ Protooncogenes can stimulate cancer but does not ALWAYS lead to cancer (can become oncogenes) 2 pathways: 1.​ Sufficient cyclin → normal cell cycle 2.​ P53 inhibit → Apoptosis restrained 3.​ Tumor suppress tumours when active (no cancer) Suppressor Gene 2 pathways: 1.​ Inhibit cyclin → Restrain cell cycle 2.​ Promote p53 → Promote apoptosis  -​ p53 Tumor-suppressing gene (transcription factor) Master regulator for cell cycle (checks for issues): Anything that promotes bad DNA WILL form cancer cells P53 helps to regulate DNA replication + repair, if the first repair does not go well (ie. if there are multiple nuclei) p53 will fix again, and help produce new cells, which will start sending destruction signals. (activation of CDK inhibitor) Abnormal p53 will result in cell dividing without repairing damaged DNA -​ Accumulated damaged cells can become cancerous 1.​ Germline mutation A change in the DNA sequence that can be inherited from either parent (from gametes) Certain populations are at a higher risk of cancer Mutation is present in every cell of the body. -​ higher risk of developing cancer than somatic 2.​ Somatic mutation - A change in the DNA sequence in cells other than sperm or egg - The mutation is present in the cancer cell and its offspring, but not in the patient’s healthy cell - can occur in any of the body's cells except the germ  cells (sperm and egg) and therefore are not passed on to children. 3.​ Spontaneous Bases pair with the wrong match cause mutation Mutation Transition (safe) purine → purine / pyrimadine → pyrimadine Transversion (changing energetics, dangerous): purine → pyramidine / pyrimadine → purine Purines: A, G Pyramidines: C,T all gods (ag) talk chit (tc=pyridines=longer time to replicate) 4.​ Chromosomal Types: Mutation 1.​ Rearrangement: Alter structure a.​ Inversion: flipping up and down around the centromere -paracentric → outside centromere -Pericentric → around centrom ere b.​ translocation: balanced/unbalanced -​ Unbalanced: loss of a part of one chromosome and/or a gain of part of one chromosome c.​ Insertion → block one of more base pair added d.​ Duplication → can be tandem or inverted -​ Tandem: repeats are repeated copies which lie adjacent to each other -​ Inverted: the tails are head-to-head e.​ Deletion → block of 1 or more bp lost -​ Terminal: a deletion that occurs towards the end of a chromosome. -​ Interstitial: a deletion that occurs from the interior of a chromosome f.​ Substitution → replacement of a base by another base 2.​ Aneuploidy: Alters # of chromosomes 3.​ Polyploidy: Alters # of sets/pairs of chromosomes -​ Aneuploidy irregular number of chromosomes Genetic selection at the level of single cells P - short chromosome arm Q - long chromosome arm  5. Point Mutation One nucleotide is mutated Point mutations can have positive, negative, or zero effects on the protein. Epigenetics plays a role in the development and passing on of mutations (environmental role in cancer development) Mutagens anything that causes mutation (leading to carcinogenesis + tumour formation) -​ Carcinogen anything that causes cancer Examples: Mutagen that causes carcinogenesis and tumor Chemical - aflatoxins formation Biological - Retroviruses Physical X-ray Irradiation ALL CARCINOGENS ARE MUTAGENS NOT ALL MUTAGENS ARE CARCINOGENS -​ Clastogens Mutagen that causes chromosome breaks, deletions, Examples: and rearrangements Chemical - bleomycin Biological - HIV virus Break, delete, rearrange = broken clasp Physical - UV waves -​ Teratogens Mutagen that causes congenital malformations Examples: Chemical - Valproate birth defects in utero → months old Biological - Toxoplasma gondii (cats) Physical - X-ray irradation teRATogen.. Baby = rat  -​ Non-specific Non-specific damage to the genetic material Examples: mutagens Chemical - Innumerable types Biological - Toxoplasma, viruses Physical - X-ray irradation -​ X-rays Non-chemical mutagen DNA breaks → GCR (deletion, inversion, translocation) -​ UV lights Non-chemical mutagen that dimerizes nucleotides and nicks DNA DNA nicks (chips in one strand of DNA) are enough for the error proteins to see there is something wrong with what it's trying to copy and initiate programmed cell death Error-prone dimers cause roadblocks in replication Translesion polymerase makes substitutions Form a dimer when adjacent molecules fuse -​ Intracalators Single nucleotide insertions and deletions during replication Any compound that inserts itself between base pairs (INTRAcalator) -​ Base/nucleotide Incorporated during replication instead of normal nucleotide (substitutions) analogs Chemical Mutagen Adds to existing nucleotides, changes their binding capacity (Insertion) Reaction and alteration of bases in DNA leads to substitutions during replication -​ Hydroxylating Add -OH → hydroxyl group to a base agents -​ Alkylating agents Ad ethyl (-CH2-CH3) or methyl (-CH3) group to a base  -​ Deaminating Remove amine groups (-NH2) agents Cellular Response + Therapies 1.​ Endogenous DNA -​ Spontaneous base changes damage -​ Replication Errors -​ Oxygen Radicals Leads to: 1.​ Blocked transcription and replication 2.​ Cell cycle delay/arrest → cell death 3.​ Aging 4.​ Cancer 2. Environmental -​ Chemical mutagens (exogenous) DNA damage -​ Cytotoxic agents -​ UV and ionizing radiation Leads to: 1.​ Misreplication, aberrant chromosomal segregation 2.​ Mutations, chromosomal aberrations 3.​ Cancer 1.​ Base excision Repairs Spontaneous damage Repairs individual bases using glycosylase flips and snips Excited about being spontaneous 2.​ Mismatch repair Repairs DNA copy errors (faulty base pairs) A system of enzymes finds and removes faulty strands 3.​ Nucleotide Repairs damage due to chemicals + radiation excision (NER) Thymine dimer Exonuclease finds damage, removes 12-nucleotide strand pathway used by mammals to remove bulky DNA lesions such as those formed by UV light -​ Waburg process Describes the use of lactic acid as the primary form of energy Usually, accumulations of acid (fermented lactic acid) will cause damage, however, cancer cells are adaptive to acidic environments -​ Kaplin-meier Used to analyze survival rates graph/curve X-axis → ALWAYS time Y-axis → proportion of population Points are in step-wise decrease Grouping variable: treatment or exposure -​ Having low or high cyclin E levels Effect: change or no change Interpreting: Flatter slope: a lower event rate and therefore a better survival prognosis. Plateaus: periods of relatively stable survival. Term Definition Purpose/ Examples Cell Cycle Cell cycle G0 (G-naught): Quiescent (lowest metabolic phase, but metabolism is not zero (only 0 when dead)) Restriction Point G1: DNA preparation for cell division All cellular contents other than chromosomes are duplicated G1/S checkpoint S: duplication of DNA (chromosomes) -​ Replication forks (copying in 2 different directions) -​ Pyrimidines take longer to replicate G2: Error checking DNA Repairing damaged DNA G2/M checkpoint M: mitosis Spindle Assembly Checkpoint Cytokinesis: The cytoplasm of a single cell divides into two daughter cells -​ Restriction point Regulate initiation of DNA replication, without it, cells cannot replicate It cannot be bypassed - a precursor to checkpoints  -​ G1/S checkpoint DNA error proteins check for any copying error in G1 before it goes to S. “Is the environment favourable?” (correct growth and resources?) Rb regulates proteins at the G1/S phase to prepare for DNA synthesis In its active, dephosphorylated state, Rb binds to transcription factors like E2F, blocking the production of proteins necessary for the G1/S transition -​ G2/M checkpoint checking for duplication errors in newly synthesized DNA at the end of G2 before it goes to mitosis. “Is all DNA synthesized?” “Is the environment favourable?” (correct growth and resources) G2-M Transition influenced by: cell size DNA damage DNA replication Mitosis PMAT (Phat male ass, thick) Where the cell divides Uses phosphorylated M cyclins to break down the membrane -​ Kinetochore within the centrosome, the biological sensor (looks and feels for mechanical pressure), where spindle fibres attach  The spindles go everywhere and make proteins until they attach to the kinetochore, which is enough mechanical pressure to pull them apart spindle fibres activate the kinetochore when they are fully all attached which sends a signal to pull the fibres back -​ Early Prophase parent cell chromosomes (duplicated during the S phase) condense and become thousands of times more compact. Envelope breaks down -​ Late Prophase Spindles separate into two poles -​ Metaphase chromosomes align along the cell equator -​ Metaphase-Interpha Check if all chromosomes are attached to the spindle/chromosome alignment before transitioning to anaphase se (Spindle Assembly) Aligning duplicated chromosomes by attaching them to bipolar attachments to the spindle. Transition The sensors of this checkpoint are present in the kinetochore Checkpoint APC/C Cofactor (CDC20) is inhibited unless there is equal tension If spindles are not 50/50 it will program itself to die CDC20 when active inhibits 'securin' which then enables the separation process  -​ Anaphase each chromosome's sister chromatids separate and move to opposite poles of the cell (centromeres) -​ Telophase formation of a new nuclear membrane around each group of chromosomes CYCLINS AND CDKs Cyclin-dependent kinase - key regulator protein of the cell cycle (CDK) -Enzyme (catalyze reaction) that binds to specific cyclins. - Carry the energy molecule (P) but cannot pass it off without cyclins present When all three are bound together, they will either activate or inactivate a specific protein to regulate the cell cycle CDK is recycled throughout phases (CDK can be used with any cyclin) Checkpoint inhibitors = CDK inhibitors -​ Mechanisms to To Prevent cell cycle: prevent cell cycle 1.​ Get rid of cyclin (inhibit binding of cyclins) 2.​ Inhibit active site for CDK  3.​ Degrade cyclins -​ Cyclin - key regulator protein of the cell cycle MCyclin: Mitosis when they bind to CDK -​ Too much leads to cell death SCyclin: Synthesis Cell phase transition specificity comes from cyclin Cyclin gets degraded after each phase completion (one-time use, each phase has its own cyclin),  Cell cycle and checkpoint genes are found misregulated/mutated in cancer -​ Phosphorylation activating a protein Once phosphorylation occurs, the S phase can occur P is carried by CDK -​ Cyclins and Cancer Cancer is partly a disease of uncontrolled proliferation. Cell checkpoint genes are found misregulated/mutated in cancer. -​ Doxorubicin The gold standard for chemotherapy → CDK inhibitor Non-selective for cancer inhibits CDK on all cells including healthy ones Negative Regulation Rb as a negative regulator Normal: phosphorylation = active Negative regulation: Dephosphorylation = dysfunctional, regulates the cell cycle -​ Retinoblastoma is produced when it is dysfunctional/mutated To pass cell cycle checkpoints, positive regulators must be activated, and negative regulators must be deactivated. P TURNS IT OFF INSTEAD OF ON -​ Rb: retinoblastoma Regulates proteins at the G1/S phase to prepare for gene DNA synthesis In its active, dephosphorylated state, Rb binds to transcription factors like E2F (E2F cannot bind to DNA), blocking the production of proteins necessary for the G1/S transition. Cel growth triggers the phosphorylation of Rb, which releases E2F, which binds to the DNA and turns on gene expression, advancing the cell cycle Term Definition Image  TYPES OF CELL DEATH Types of Cell Death Regulated (RCD): Specific proteins involved in telling cells to die (everything but necrosis) Unregulated or accidental (NRCD): death is not initiated by specific proteins (Necrosis) Regulated Non-Necrotic (RNNCD): membrane remains intact (apoptosis + autophagy) Regulated Necrotic (RNCD): membrane does not remain intact (Ferroptosis, Pyroptosis, Necroptis) -​ Ferroptosis -membrane disruption due to accumulation of iron -small mitochondria -​ Pyroptosis - Heat-induced cell death - due to inflammation - core can withstand a change within - in brain > 2 degrees -​ Necroptosis - decaying tissue, accumulation of necrotic cells Progressive disintegration of cell structure -​ Initiated by overwhelming stress -​ Usually elicits an acute inflammatory cell response -​ neutrophils may be present -​ Autophagy Cell degrades and eats part of itself A good part of cell death. chews off bad parts and makes them good. Too much results in cell death Membrane blebbing and lysosomal activity  -​ Necrosis - Loss of functional tissue - caused by accidental injury/overwhelming stress - Impaired organ function, transient or permanent -Progressive disintegration of cell structure -Usually elicits an acute inflammatory cell response (neutrophils present) -membrane blebs and swelling of ER and mitochondria - can be reversed to a certain extent (until progressive injury, where plasma membrane, organelles, and nucleus break down and leak out) Apoptosis (PCD) Removal of damaged or unnecessary cells tightly regulated pathway of cell death (molecules associated, has control) -​ Controlled by very specific genes -​ Fragmentation of DNA, nucleus -​ Chromaden condenses, blebs form and apoptotic bodies are released (membrane flowers, bubbles and forms individual packages) -​ Apoptotic bodies are phagocytized -​ No neutrophils (innate immune cells) When it starts to degrade itself, it neatly packages itself up Happens under normal physiological conditions, not always cancer-related -​ Signs of apoptosis 1.​ Blebbing (before) → recruits the immune system - No blebbing → leakage into environment 2.​ Apoptotic bodies -​ Apoptosis Process 1.​ The cell is damaged, stressed, or triggered by signals to begin apoptosis 2.​ The cell begins to shrink and form blebs. Proteins are activated to break down cellular components 3.​ Enzymes break down the nucleus and the cell emits signals to attract macrophages (“Find me” signals) 4.​ The cell breaks into several smaller pieces containing cell components and destroyed nucleus 5.​ Macrophages recognize cell parts and remove them from the body (“eat me” signal) 6.​ post-engulfment consequences (i.e. release of anti-inflammatory cytokines) -​ Apoptosis In Utero 1. digit formation - lack of apoptosis = syndactyly (webbed fingers) 2. Morphogenesis → creation of shape -​ Too much apoptosis = cleft palate, hole in the heart 3. In the brain → losing neurons (pruning networks) -​ Gets rid of glutamate (released when cells are not being used anymore), unnecessary energy used up -​ Cell death matches the number of nerve cells to the number of target cells -​ Apoptosis in -​ Normal cell turnover (Regulate new cell/old cell Adults ratio) -​ Tissue homeostasis -​ Induction and maintenance of immune tolerance -​ Development of the nervous system -​ Endocrine-dependent tissue atrophy -​ Elimination of activated, damaged and abnormal cells intrinsic pathway death signal comes from inside of cell 1.​ Increased mitochondrial permeability with the release of pro-apoptotic molecules into the cytoplasm (cytochrome c). 2.​ Synthesis of anti-apoptotic molecules (Bcl-2) promoted by Growth factors. 3.​ Mitochondrial membrane becomes permeable and proteins that activate caspase leak out. -​ The initiator then executioner caspases Permeability Anti-apoptotic Caspase Phat ant cheeks -​ When cells are deprived of growth factors or subjected to stress anti-apoptotic molecules (Bcl-2) are lost. -​ Bcl-2 is over-expressed in most follicular B-cell Lymphomas, allow abnormal cells to proliferate. -​ Caspase (enzyme) ONLY THING THAT CAUSES APOPTOSIS. OTHER THINGS TRIGGER IT BUT THIS IS THE ONLY ONE Caspases= proteases (catalyze the breakdown of other proteins) -​ Regulates apoptosis - born inactive, all are synthesized as inactive proenzymes (zymogen) - 14 types: 10 apply to mammals - signalling/initiator → 2, 8, 9, 10 - begins apoptosis - effector/executioner → 3, 6, 7 (3 is the main finisher) - finish apoptosis - inflammatory → 1, 4, 5 -when a protein breaks down another protein = causing inflammation  -​ Cytochrome c regulated by P53 and alteration of cell membrane -​ protein within the electron transport chain (mitochondrial membrane) -​ Pro-apoptotic proteins include Bax, Bak, Bid, Bad, Bim, Bik, cytochrome C -​ Initiator of next steps when it leaves the mitochondria -​ High levels within cytoplasm = indication of activation of intrinsic apoptotic pathway (must wait for effector caspase) -​ Low concentration in cancer cells, which are high in antioxidants (cytochrome c is an oxidant) -​ When the mitochondrial membrane potential is changed (change in charge), or heated (inflammation) the membrane will become permeable for the release of cytochrome c -​ BCL-2 when activated, keeps cells from not dying (inhibition of (regulated by Bax/Bak) cell death) When inactivated, tells the cell to die -​ When overexpressed, the abnormal cell proliferates -​ The control & regulation of apoptotic mitochondrial events -​ Anti-apoptotic proteins include Bcl-2, Bcl-x, Bcl-XL, Bcl-w -​ The main mechanism of action of the Bcl-2 family of proteins is the regulation of cytochrome c -​ For every cytochrome C, there’s one BCL2 release from the mitochondria via alteration of mitochondrial membrane permeability. extrinsic pathway death signal comes from outside of the cell death ligand (signal) must bind to a death receptor (i.e. TNF receptor) - death receptor must have a death domain Inflammation does not affect the extrinsic pathway Mostly affected by viral proteins 1.​ Binding of trimeric FasL to Fas 2.​ Trimerization and clustering of Fas 3.​ Recruitment of Fas-associated death domain (FADD) to Fas 4.​ Recruitment of caspase-8 to FADD 5.​ Formation of Death-Inducing Signaling Complex (DISC) 6.​ Activation of caspase-8 (autoactivation) 7.​ Activation of effector caspases 8.​ Apoptosis Binding FasL to Fas → Trimerization of Fas → FADD Recruitment → Caspase-8 Recruitment → DISC formation → Caspase-8 activation → Effector caspase activation → Apoptosis -​ Death receptors First step in Extrinsic Pathway (binds to death -​ members of the tumour necrosis factor (TNF) receptor superfamily. ligand) -​ Death receptors have a cytoplasmic domain of about 80 amino acids called the “death domain”. -​ This death domain plays a critical role in transmitting the death signal from the cell surface to the intracellular signalling pathways. -​ Membrane flipping -​ Pieces of membrane flip (inside out) and initiate cell death -​ Death receptors are now inside the cell, ligands bind to them, cell dies -​ Cholesterol keeps phospholipids together, flipping happens when there is a deficiency -​ Ketosis: depleting cholesterol storage: likely to get cancer via membrane flipping Which characterizes cancer cells? A. Poorly differentiated B. Metastasis C. Infiltrative growth D. Poor cell cohesiveness E. All of the above Metastasis is ______ A. Alteration in normal cell growth B. Growth of benign or malignant cells C. Mutational D. Ability to establish a secondary neoplasm at a new site Which is/are not malignant? A. Glioma B. Adenocarcinoma  C. Rhabdomyoma D. Leukemia E. A and C CIS is: A. Preinvasive B. Glandular or epithelial lesion C. Teratoma D. Carcinoma that has broken through BM E. Both a and b are correct