237b tumor invasion and metabolism

Question 1

tumor cells - how do solid tumors get their energy/ATP?

Answer 1

Warburg metabolism: aerobic glycolysis - no oxidative phosphorylation

thus produce lactate (from pyruvate) and skip TCA cycle (only get 4 ATP as opposed to 36 ATP)

Question 2

multi event carcinogenesis - spread and switch of metabolism

Answer 2

normal

hyperplasia

carcinoma in situ - still use oxidative phosphorylation

invasive carcinoma - Warburg effect –> allows invasion of basement membrane (via collagenase and hydrolases) and malignancy; Also see change in mitochondria appearance

metastatic

Question 3

Do tumor cells need insulin to act in feed manner?

Answer 3

tumor cells don’t need insulin to turn on IGF-1 –> PI3K pathway –> Akt –> proliferation, growth, metabolism

many genes are mutated such that the cells always think they are in the feed state and pathway is active

Question 4

does insulin cause phosphorylation or dephosphorylation?

Answer 4

Phosphorylation via Kinases –> fed metabolic state –> pro metabolism, proliferation, aging, cancer

Question 5

warburg metabolism in cells - what happens to glucose?

Answer 5

glucose –> PEP (1) –> pyruvate (2)–> lactate (very inefficient)

enzyme 1 –> PKM2: allows entry into mitochondria (TCA cycle) but Warburg shunts pushes into lactate pathway (tumor cells are thus acidic) because PKM2 is so upregulated that the TCA cycle is overwhelmed and can’t deal with all the excess pyruvate.

enzyme 2 –> LDHA

Question 6

PET scan - how does it work?

Answer 6

radioactive glucose is given to patient

measure radiation to determine which cells take up most glucose

warburg effect allows this to work

Question 7

mitochondria appearance in tumors?

Answer 7

cristolysis - loss internal membrane folds

see appearance change as tumor changes to a carcinoma

Question 7

mitochondria appearance in tumors?

Answer 7

cristolysis - loss internal membrane folds

see appearance change as tumor changes to a carcinoma

Question 8

what are the biggest risk factors for cancer? what are 2 proteins that are anti-metabolism and make you live longer?

Answer 8

aging
metabolism (calorie restriction reduces cancer and makes you live longer)

2 proteins that are anti-metabolism/longevity:
PTEN
Sirtuins