Cell Communication & Cancer

plasma membrane functions

• determines composition of cytoplasm by isolation from external environment

• controls interactions between cell and environment (cell - cell or cell - matrix attachments)

plasma membrane structure

• lipid (~50%) - forms phospholipid bilayer; major structural component

• proteins (~50%) - imbedded within bilayer to carry out specific functions, such as attachment, transport, and signaling; have lateral mobility

• carbohydrate (~5-10%) - glycoproteins and glycolipids on external face of membrane; cell-cell interactions

peripheral membrane proteins

associated via other plasma membrane proteins (not associated with hydrophobic interior)

integral membrane proteins

imbedded within the plasma membrane interior

functions of membrane proteins

• transport

• enzymatic activity

• signal transduction

• cell-cell recognition

• intercellular joining

• attachment to the cytoskeleton and extracellular matrix (ECM)

unsaturated fatty acids

have double bonds that form bends, causing hydrocarbon tails of the inside of the plasma membrane to kink, preventing packing and enhancing membrane fluidity

cholesterol in animal cell membrane

reduces membrane fluidity at moderate temperatures by reducing phospholipid movement; at low temps, hinders solidification by disrupting the regular packing of phospholipids

passive transport

molecules move across cell membrane without energy, from an area of high concentration to an area of low concentration (until equilibrium reached); gases, small non-polar molecules, polar molecules

• simple diffusion

• facilitated diffusion

• osmosis

facilitated diffusion

passive transport across a plasma membrane with help of a membrane protein (ex: aquaporins)

• large macromolecules (ex: glucose), polar molecules, and charged molecules

osmosis

passive transport diffusion of water across plasma membrane

• from higher free water concentration to lower free water concentration

isotonic solution

(osmosis)

equal concentration of water on both sides = no net movement

hypertonic solution

(osmosis)

higher free water concentration on the inside = water leaves cell = shrivel

hypotonic solution

(osmosis)

higher free water concentration on the outside = water enter cell = cell can swell and lyse (explode)

• girlie gets huge

active transport

requires energy to move from low to high concentration against the gradient

• bulk transport (endocytosis, exocytosis)

exocytosis

bulk active transport where cell expels large macromolecules

endocytosis

cell intaking materials

• pinocytosis (fluid with solutes; “cell drinking)

• phagocytosis (large solids; “cell eating”)

• receptor mediated endocytosis (molecules based off ligand)

cell communication

• signal molecules (cytokines, growth factors, hormones) = words

• receptors = ears

• signal pathways = nerves

• nucleus = brain

endocrine signaling pathway

a cell targets a distant cell through the bloodstream; “cell shouting”

• hormones and other signaling molecules secreted

• ex: estrogen produced by ovaries acts on breast and uterus

paracrine signaling pathway

a cell targets a nearby cell; normal “cell conversation”

• cytokines and growth factors released by one cell act on adjacent

juxtacrine signaling pathway

a cell targets a cell connected by gap junctions; “tapping your friend on the shoulder”

• some signal molecules inserted into membrane

• 2 cells touch, one cytokine activates receptor on adjacent cell

• common mechanism for growth factors

autocrine signaling pathway

a cell targets itself; “cells talking to themselves”

• release signals that bind to receptors on same cell

• happy cells make growth factors that stimulate proliferation

• important in cancer

• classes: steroids (intracellular receptors) and polypeptides (cell surface receptors)

acromegaly

hormonal disorder when pituitary gland produces excess growth hormone (GH)

• can result in premature death

• slow onset = infrequently correctly diagnosed

signal transduction pathway steps

1. signaling molecule binds receptor

2. signal cascade triggers several reactions

3. required response achieved

G protein-coupled receptors

activate guanine nucleotide binding proteins (G proteins)

• include receptors for neuropeptides and hormones in brain; receptors for sight, taste, and smell, and many polypeptide growth factors

• attached to cytoplasmic side of membrane, can move

• inactive with GDP; GTP binds to activate = shape change = G protein activate = binds to other enzyme = cellular response

• cholera locks G-proteins in active forms (prevent salt + water reabsorption = dehydrate)

human epidermal growth factor receptor 2 (HER2)

tyrosine kinase; key component for regulating normal cell growth; too much produced = over expression = increased cell growth = aggressive breast cancer

herceptin

antibody that binds HER2 receptors on plasma membrane, preventing receptors from receiving growth signals

ion channel receptors

ligand binds receptor, opening channel, allowing ions to diffuse across membrane

steroid hormones

lipophilic molecules that pass through cell membrane easily; receptors usually in cytoplasm or nucleus (transcription factors)

• ex: estradiol, testosterone, other derivatives of cholesterol

phosphorylation in signaling

• kinases required for protein phosphorylation

• phosphatases required for dephosphorylation

second messengers

non-protein water soluble signaling molecules

• adenylyl cyclase removes 2 phosphates from ATP, making it cAMP

• phosphodiesterase converts cAMP to AMP

cell cycle checkpoints

monitor internal conditions; “brakes”

• ex: is the cell large enough, has DNA been replicated, has every chromosome attached to spindle fiber

cell cycle stimulators

accelerator of cell cycle

• cell growth stimulators (external factors)

• ex: growth factor hormones; hormone receptors

carcinogens

• radiation - UV, X-rays

• chemicals - cigarette smoke, nitrate and nitrate preservatives, barbecuing (mutagenic chemicals), benzoyl peroxide (acne products)

• infectious agents - human papillomavirus (HPV), Helicobacter pylori (bacteria in contaminated food)

cancer

broken regulation of cell cycle

properties of cancerous tumor cells

• reduced need for growth factors (make autocrine ones)

• protease secretion (digest extracellular matrix = easier metastasize)

• less adhesive (fewer surface adhesion molecules = move around)

• lose contact inhibition (grow on top of other cells; foci piles of cells)

• angiogenesis (develop blood vessels for supply inside tumor)

• resist apoptosis/programmed cell death (resist chemotherapy/ radiotherapy)

carcinoma

arise from epithelial cells; more than 90% of cancers

• solid tumors: lung, breast, colon

sarcoma

arise from connective tissue including bone, muscle, and fibrous tissue; rare <2% of cancers

• ex: fibrosarcoma, osteosarcoma

leukemias/lymphomas

arise from blood cells or immune cells, respectively; make up 8% of total cancers

lung cancer

lung cells interact with capillaries for gas exchange, but mutated lungs can’t properly do this

• largest carcinogen associated: smoke

cervical cancer

cervix cells constantly replacing themselves can lead to cancer

• pap smear - take sample from cervix to test

prostate cancer

prostate gland above the penis produces key androgen hormone, key in semen production

cancer treatments

1. surgery (slash)

2. radiation (burn)

3. chemotherapy (poison)