Oncogenes and signalling pathways Flashcards
(30 cards)
What are proto-oncogenes?
Genes that normally regulate cell growth and differentiation; can become oncogenes when mutated or misregulated.
How do proto-oncogenes activate transcription?
Through products like transcription factors (e.g., Myc, Fos, Jun) that bind DNA and promote expression of cell cycle genes.
Which transcription factor family is formed by Fos and Jun?
AP-1 (activator protein-1)
What happens when c-Myc is amplified?
Overexpression drives uncontrolled cell proliferation (e.g., in neuroblastoma, SCLC).
How is Ras activated?
By GEFs like Sos, which replace GDP with GTP on Ras following RTK activation.
How is Ras inactivated?
By GAPs (e.g., NF1), which stimulate GTP hydrolysis.
What does active Ras-GTP recruit?
Raf to the membrane → initiates MAPK cascade.
What happens when Ras is mutated (e.g., codon 12)?
It can’t hydrolyze GTP → remains active → promotes cancer.
What is the MAPK pathway sequence?
Ras → Raf → MEK → MAPK → transcription factors → cell proliferation.
What do integrins do?
Connect cells to ECM, regulate motility, and signal through pathways like Ras-ERK.
What is “inside-out” signaling?
Cytoplasmic signals change integrin conformation to increase ligand affinity.
What is “outside-in” signaling?
ECM binding activates intracellular signaling for migration, survival, etc.
Name integrin signaling proteins.
FAK, Src-family kinases, ILK, paxillin, vinculin.
What is TGF-β’s dual role?
Tumor suppressor (induces apoptosis); tumor promoter (invasion, EMT).
Which genes are up/downregulated by TGF-β?
Up: p15, p21, MMPs, Snail; Down: c-Myc.
What does the β-catenin destruction complex do?
Targets β-catenin for degradation (APC, axin, GSK3, CK1).
What happens when Wnt binds Frizzled + LRP5/6?
Inhibits degradation complex → β-catenin accumulates → transcriptional activation.
Which residues promote β-catenin degradation?
Ser33, Ser37, Thr41 (phosphorylated by GSK3β).
What physiological functions involve GPCRs?
Neurotransmission, immunity, cardiac function, hormone release.
What does PGE2 do in colon cancer?
Activates EP2 receptor (Gαs-coupled) → promotes tumor progression.
What causes Gorlin syndrome?
Loss-of-function mutation in PTCH1 → constitutive Hh activation.
Tumors linked to Hh pathway dysregulation?
Basal cell carcinoma, medulloblastoma, rhabdomyosarcoma.
List the 5 models of Hh pathway activation in cancer.
Type 1: ligand-independent, Type 2: autocrine, Type 3: paracrine, 3b: reverse paracrine, CSC model.
What are Notch pathway target genes?
Hes1/5, Hey1, CD25, GATA3, c-Myc, cyclin D1, p21, Bcl2, etc.
