Introduction to hallmarks of cancer Flashcards
(24 cards)
What is senescence and quiescence
senescence is irreversible cell cycle arrest driven by a number of different mechanism
quiescence is cells in the state of not dividing
How does a normal cell transform tumorigenic cell
○ Disabling detection mechanisms
○ Inactivating negative cell cycle regulators
○ Overactivation of positive cell cycle regulators
○ Inactivating genome stability factors
What are the major types of cancer
carcinomas, sarcomas, lymphomas, myelomas, leukemias
What are the subtypes of carcinomas
adenocarcinoma in lung, breast, prostate and colon cancer
Squamous cell carcinoma or skin cancer
Where do sarcomas arise
in supporting tissues of body
where do lymphomas arise and what are the main types
arise in WBC and are divided into hodgkin’s lymphoma and non-hodkin’s lymphoma
where do myelomas arise
in antibody-producting plasma cells
where do leukemias arise and what are the main types
they arise in immature blood cells that grow in BM and accumulate in blood stream
can be categorised into actue leukemia, chronic leukemia, lymphocytic (affect lymphocyte), myelogenous leukemia (affect other cell types )
what are the main cause of cancer
tobacco, virus such as HPV, Hepatitis B and C
bacterial infection such as H.pylori and ageing, UV light
What are the six hallmarks of cancer
evading apoptosis self-sufficiency in growth signals insensitivity to anti-growth signals tissue invasion and metastasis limitless replicative potential sustained angiogenesis
What cell types are linked to cancer
Cancer stem cells – progenitor cells from which the tumour is derived
• Immune inflammatory cells – innate immune cells that secrete growth factors and
cytokines that promote tumorigenesis
• Cancer associated fibroblast – cell that secretes paracrine factors to promote
tumorigenesis
• Endothelial cells – form the blood vessel walls
• Pericyte – wrap around endothelial layers to regulate capillary blood flow
• Invasive cancer cells – cells that acquire the ability to move out of the original
tumour site
What three mechanism can cells undergo for self-sufficiency in growth signals
Alteration of extracellular growth signals - Cancer cells acquire the ability to make their own growth factors, creating a positive feedback signalling loop
Alteration of response to growth factors - cancer cells overexpress receptors that allow them to become hyper-responsive to levels of growth factors that would not normally trigger growth.
Alteration of intracellular response - I n some cancer cells, the downstream cytoplasmic components that receive and process growth factor signals can signal without ongoing stimulation by their normal upstream regulators.
Describe insensitivity to anti-growth signals
In cancer cells, when DNA is damaged, RB is damaged which is a tumour suppressor and cannot activate the checkpoint and damaged cell will continue to divide - avoiding apoptosis
Describe evading apoptosis
cells avoid apoptosis due to absent or defective p53
Describe limitless replicative potential
cells have a hayflick limit where they become senescent
cancer cells upregulate telomerase to avoid telomere shortening and triggering of senescence
Describe sustained angiogenesis
process which cells trigger formation of new blood vessels so tumour can grow and spread
tumours release VEGF to activate endothelial cells to form new blood vessels
What are the stages in tumour progression pathway in sustained angiogenesis
- dormant- tumour start growing as avascular nodules until they reach stead state level of proliferating and apoptosing cells
- Perivascular detachment and vessel dilation
○ The initiation of angiogenesis, or the ‘angiogenic switch’, has to occur to ensure exponential tumour growth.
○ The switch begins with perivascular detachment and vessel dilation. - Onset of angiogenic sprouting
○ Perivascular detachment and vessel dilation is followed by angiogenic sprouting
○ Continuous sprouting; new vessel formation and maturation; Recruitment of perivascular cells
○ New vessels form and mature, and there is recruitment of perivascular cells
○ Tumour vasculation
○ Blood-vessel formation will continue as long as the tumour grows, and the blood vessels specifically feed hypoxic (areas where there is inadequate oxygenation) and necrotic (dying) areas of the tumour to provide it with essential nutrients and oxygen.
- Perivascular detachment and vessel dilation
describe metastasis
cancer cells can invade surrounding tissues and vessels and transported by circulaory and reinvade and grow in new location
How do cell carry out metastasis
· In order to break away from tumour
○ Cell overcome mechanisms that cause them to adhere to their neighbours
○ Adhesion such as e-cadherin is downregulated in cancer
may also alter expression of integrin protein
What is the 7th hallmark and its characteristics ?
Deregulating cellular energetics
· Warburg effect - even in the presence of oxygen, cancer cells can reprogram their glucose metabolism and thus their energy production, by limiting their energy metabolism largely to glycolysis, rather than the much more efficient oxidative phosphorylation pathway
○ Leading to aerobic glycolysis
· Leads to increased generation of additional metabolites that benefit proliferating cells
What is the 8th hallmark and its characteristics ?
Avoiding immune destruction
· By switching off the expression of cell surface antigens that would identify them to the immune system as dangerous
What are the two enabling characteristics
genome instability and tumour-promoting inflammation
describe genome instability
DNA methylation to inactivate tumour suppressor genes
eg. BRCA1 and/2, p53 and Rb which are involved in DNA repair, halting cell cycle upon DNA damage
Describe tumour promoting inflammation
· Supplies bioactive molecules to tumour microenvironment, including growth factors to sustain proliferative signalling
· Release ROS which are actively mutagenic
