Lecture 17: Cancer as a Metabolic Disease Flashcards
what part of the mitochondria is abnormal in cancer
missing cristae → can’t conduct oxidative phosphorylation → cells need to ferment (get energy from a non-oxidative source)
which high profile people did GBM mitochondria kill
Ted Kennedy, Bo Biden, John McCain
all major cancers have abnormalities in the number and structure of mitochondria. how do those cells survive? what energy do they need to grow?
- fermentation, which is ATP in hypoxia (“w/o oxygen”)
- because they have abnormalities in their mitochondria structure and function
role of mitochondrial lipids in electron transport chain function
every tumor has an abnormal composition of cardiolipin
abnormal composition/distribution of cardiolipin > disrupts ETC’s structure/efficiency in producing ATP through oxidative phosphorylation
role of cardiolipin:
cardiolipin in the inner mitochondrial membrane stabilizes and organizes key ETC protein complexes to ensure efficient electron transfer and ATP production
tumors and cardiolipin abnormalities:
in cancer cells, cardiolipin often has an abnormal composition or distribution. this can disrupt the ETC’s structure and reduce its efficiency in producing ATP through oxidative phosphorylation
inefficient oxidative phosphorylation in cancer:
most cancers rely more on glycolysis for energy (even in oxygen’s presence, known as the Warburg effect) because their oxidative phosphorylation is inefficient, partly due to defective cardiolipin
cardiolipin
lipid enriched in the inner membrane of the mitochondria
where and when else does the body ferment?
- RBCs
- muscle cells (for a bit)
- after a heart attack (the body will temporarily ferment because it will be filled with lactic acid and succinic acid instead of blood)
carcinogen: what is it and how does it impact mitochondria?
- cancer-causing chemical
- enters mitochondria and inhibits it from producing energy efficiently
reactive oxygen species (ROS)
- chronically damages the ability of the mitochondria to function
- carcinogenic
- mutagenic (“the ability to cause a permanent change in an organism’s genes”)
sleep apnea
not breathing sometimes while sleeping > intermittent hypoxia > damage to oxidative phosphorylation > development of dysregulated cell growth driven by fermentation (must happen chronically (“all the time”) in order for this to happen though)
C reactive protein
- marker in blood for inflammation
- significant relationship between obesity and cancer
what are the consequences of chronic inflammation
chronic inflammation > damage in oxidative phosphorylation > mitochondria becomes damaged > over time, the mitochondria relies on fermentation
BRCA1 mutation
mutation that damages oxidative phosphorylation
* Angelina Jolie removed her breasts because she had this gene for breast cancer
why does the dogma state that cancer a genetic disease?
many cancers have mutations in the nucleus
where do the mutations in cancer come from?
the reactive oxygen species (ROS) produced by the abnormal mitochondria. the mutations aren’t the cause of cancer, but an effect of cancer
dogma vs. reality of cancer theory
dogma: mutations in the nucleus cause disregulated cell growth
reality: the reactive oxygen species (ROS) produced in the mitochondria cause the mutations
cancer
disregulated cell growth, or cells that are growing that are no longer in control
what happens when the mitochondria becomes corrupt?
the mitochondria is the organelle that regulates the stability of the cell, but when it becomes corrupted, the cell falls back on a disregulated path of growth that leads to cancer
the relationship between cancer malignancy, mitochondria damage, and cell fermentation
the more malignant the cancer, the more damaged the mitochondria, the more fermentation the cell undergoes
apoptosis
programmed cell death, a natural process by which cells die to make room for new, healthy cells
apoptosis in cancer
cancer evades apoptosis because the mitochondria is faulty, allowing the cancer to continue to grow
what causes cancer?
abnormalities in the mitochondria in the cytoplasm cause cancer
metastasis
- involves the spread of cells of the primary neoplasm (“an abnormal growth of tissue that can be benign or malignant”) to distant organs and their relentless growth
- responsible for about 90% of all cancer deaths
- Stephen Paget’s 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the “seeds”) and specific organ microenvironments (the “soil”) still holds forth today
what kind of cancer can be surgically removed and through what method?
the spread of cancer, if localized, can be surgically removed through radiation
benign
noncancerous, localized cancer that hasn’t spread
metastatic cascade
- local invasion
- intravasation
- immune system survival
- immunosuppressive
- extravasation
- secondary tumor formation
local invasion
a group of disregulated cells invades a part of your organ
intravasation
tumor cells enter into the bloodstream and start to spread
immune system survival
we’re supposed to have an immune system that kills the renegade cells, but the immune system views the tumor cells as regular cells
immunosuppressive
the tumor cells also suppress the immune system
extravasation
tumor cells leave the bloodstream and spread to other organs
secondary tumor formation
result of the metastatic cascade; how a lung tumor can go to the spleen, liver, brain, etc.
metastasis
the spread of the tumor from its original site
macrophage fusion hybrid hypothesis of metastatic cancer
slide 9
normal epithelium > dysplasialadenoma > carcinoma in situ > macrophage fusion event > damage to fusion hybrid > intravasation > extravasation
waste products of fermentation
lactic acid and succinic acid are waste products of fermentation and the immune system tries to heal the wound (macrophages) → throw out growth factors, which make the blue cells even more aggressive
how macrophages accidentally help cancer grow
- the macrophages have the capacity to fuse with each other and other cells in the micro-environment, fusing with the tumor cell
- cancer is viewed as a wound → macrophages try to fix the wound → become joined with the tumor cell → can enter/exit the bloodstream and are accepted since macrophages are seen as normal → mitochondria becomes corrupt
how to kill cancer
target glucose and glutamine simultaneously
how to prevent cancer
prevent cancer by never letting your mitochondria get damaged → eat like a paleolithic diet
is cancer a genetic or metabolic disease?
contrary to popular belief, cancer is not a genetic disease. it is metabolic
TNM staging of cancer
T = tumor: describes size and margins of tumor
N = nodes (lymph): describes which nodes are affected
M = metastasis: describes which distant sites are affected
