Unit 3 - Cell Biology Of Cancer Flashcards
What is the normal fnx. Of CTLA-4?
Brake (down reg.) T-cell activation
What are the normal fnxs. Of PD-I?
Required for T-cell activation
Diff mechanism = brake on tumor directed T-cells
What targets both CTLA-4 & PD-I when treating cancer?
MAb = stop tumor suppressing immune response
Eg. CAR T-cell therapy
How has the molecule used in CAR T-cell therapy changed overtime?
1st gen = cytotoxicity
2nd gen = + proliferation/cytokine production
3rd gen = + survival
What are the hallmarks of cancer?
Sustained proliferative signaling
Evading growth suppressors
Activating invasion & metastasis
Enabling replication immortality
Inducing angiogenesis
Resisting cell death
What are the emerging hallmarks of cancer?
Avoiding immune destruction
Tumor-promoting inflammation
Genome instability and mutation
Deregulating cellular energetic
What are the 7 essential steps of invasion-metastasis cascade?
Localized invasion
Intravasation (into blood)
Transport
Arrest
Extravasation
Proliferation
Colonization
How do carcinomas arise?
Change in phenotype by epithelial to mesenchymal transition (EMT)
EMT gives migrating ability
What is EMT involved in? (ie. Mechanisms used by invasion metastasis cascade)
Embryogenesis
Wound healing
What are the key components of EMT?
Expression of embryonic transcription factors to change phenotype
-snail, slug, twist, zeb 1/2
Loss of e-cadherin fnx.
Loss of tight jnx.
Acquisition of motility
Protease secretion
Growth factor receptor expression
What do epithelial tight jnxs. contain that has a role in Anchorage#dependent signaling?
E-cadherin (&APC) which regulate ß-catenin (transcription factor part of Wnt)
What happens to ß-catenin upon loss of cell adhesion?
Translocates to nucleus to activate TCF/LEF family transcription factors
How are cytoplasmic levels of ß-catenin maintained?
Ubiquitin-dependent proteolysis via ß-catenin destruction complex
What gene, implicated in cancer, is a regulator of ß-catenin?
APC gene
=Familial Adenomatous Polyposis
What type of gene is APC?
Tumor suppressor gene
Unusual as has autosomal dominant mutations (normally these are oncogenes)
