BIOL408, Unit 4- apoptosis and cancer

what factors drive apoptosis?

developmental signals, tissue homeostasis, immune system development, viral infections, and tumorigenic cells

necrosis

unregulated cell death where cells burst, accompanied with inflammation

apoptosis

regulated or planned cell death where cells break down into smaller pieces that can be taken up through phagocytosis

what are other forms of programmed cell death?

pyroptosis and autophagic cell death

pyroptosis

fiery cell death with productive inflammation

autophagic cell death

autophagic vesicles take over a cell leading to cell death

why may autophagic cell death occur?

to recycle nutrients, drive out pathogenic cells, protect from reactive oxygen, or handle protein misfolding

c.Elegans

clear organisms that have known cell lineage and apoptosis counts

what happens when ced-3 is mutated in c.Elegans?

wildtype cells don't die when they are programmed to

what are the three major types of molecules involved in the apoptopic pathway?

regulators, adaptors, and effectors

regulator molecules

inhibit adaptors ( Bcl-2 and IAP)

adaptor molecules

activate effectors, leading to cell death (Apaf-1 or Fas)

effector molecules

cleave targets that initiate cell death (caspases)

caspases

family of proteases that cleave at aspartic acid sites and activate other caspases to promote cleavage of target molecules

procaspase

inactive caspase form that activate once cleaved

how is the first caspase in a cascade activated?

adaptor molecule binding

what are the two pathways for caspase activation?

intrinsic/metabolic pathway and the extrinsic/extracellular signal-molecule pathway

intrinsic/metabolic pathway

cytochrome C is released from the mitochondria, binds to Apaf-1 to activate them, bound complexes bind each other to form an apoptosome, apoptosome clusters recruit caspase clusters, cascade is initiated

external/extracellular signaling pathway

immune cells recognize target cells, Fas ligands clustered on the immune cell promote clustering of Fas receptors on the target cell once membrane-bound, Fas receptor clustering recruits adaptor proteins within the cell, adaptors lead to caspase clustering

what are the two main families of apoptopic regulators?

Bcl-2 and IAP

Bcl-2

apoptopic regulators that can promote cell death or survival

IAP

block aspartic acid residues to inhibit activation of caspases

how can external signals regulate apoptosis?

regulating death inducers or blockers

what are characteristics of cancer cells?

rapid uncontrolled division, changed cell shape, are able to inhibit or resist signaling, are less differentiated, and they promote vascular growth

what differentiates benign and malignant tumors?

the ability to invade neighboring tissues, the speed of growth, level of differentiation, and malignant tumors can reappear after removal

carcinoma

originate from gut or skin and neural epithelia

sarcoma

originate from muscle, blood, or connective tissue

leukemia

type of sarcoma originating from blood cells

what are the three factors indicated in the TNM staging?

tumor size (t1-t4), level of lymph node spread (n0-n3), and the level of metastasis (m0 or m1)

proto-oncogene

genes that promote cell division or reduce apoptosis

oncogene

mutated proto-oncogene that lead to the development of cancer

tumor suppressor genes

inhibit the continuation of the cell cycle or increase apoptosis

what happens when tumor suppressor genes are mutated?

proteins may become non-functional and allow uncontrolled cell cycle activity

what are examples of proto-oncogenes?

Ras, cdc25, IAP

what are examples of tumor suppressor genes?

MAPK phosphatase, securin, and caspases