cancer bio

oncogenes

mutated or overactive genes that drive uncontrolled growth

signal transduction

• how external signals (growth factors, ligands) are received at the membrane and translated into intracellular actions.

cell communication

keeps cells coordinated, preventing “selfish” growth that disrupts tissues

cancer

occurs when these systems break down (e.g., oncogenes hijack normal pathways

oncogenes and signaling

• Act as parts of signaling chains (ligand → receptor → cascade → cellular response).

• Promote cell division, survival, migration when deregulated.

• Example: Src, first oncogene discovered, a tyrosine kinase.

morphogenesis

shaping tissues through

morphogenesis function

• Growth

• Differentiation

• Movement

morphogenesis requires…

cell signaling, adhesion, movement

Outcomes of signaling

• Gene expression (long-term)

• Enzyme activity changes (short-term)

• Cytoskeleton rearrangement (short-term)

Paracrine

Neighboring cell secretion, Ligand binds receptor

juxtacrine

Membrane-bound ligands, Cell-cell contact

homophilic

Same ligand + receptor, Adhesion

heterophilic

Different ligand + receptor, Adhesion/signaling

Growth Control

Cells divide only as much as needed

mitogens

(growth factors) maintain balance

Serum cultures

• cells only proliferate when growth factors present.

PDGF knockout receptor

• cells live but don’t divide/migrate → receptors are essential.

Src

• First oncogene (v-src).

• Tyrosine kinase (rare type).

• Autophosphorylates + phosphorylates many targets (pleiotropy).

EGF-R

First growth factor receptor discovered

Many RTKs implicated in cancer (mutations, overexpression)

Viral Src 

• always on → uncontrolled proliferation

pleiotropy

• Autophosphorylates + phosphorylates many targets

structure of EGF-R

• Ectodomain = binds ligand

• Transmembrane domain = anchors receptor

• Cytoplasmic domain = tyrosine kinase

Ligand

Extracellular, Binds receptor, starts signaling

membrane receptor

transmembrane, recognizes ligand, activates cascade

Tyrosine Kinase

Cytoplasmic/receptor domain, Phosphorylates proteins, Growth/division

Target Proteins

Intracellular, Change activity after phosphorylation, Alter gene expression, enzymes, cytoskeleton

Growth is tightly regulated by

• extracellular signals → intracellular cascades.

Oncogenes hijack signaling →

constant “growth on” signal

Tyrosine kinases (Src, RTKs)

• central regulators of proliferation.

• main cancer drivers

Communication between cells…

maintains tissue health

Disrupted signaling →

uncontrolled growth = cancer

v-erbB

viral oncogene, deletion → receptor always active

Her2/Neu

paralog of EGF-R, amplified in breast cancer.

• Therapy: Herceptin blocks Her2.

Oncogenic activation mechanisms

• Overexpression → ligand-independent dimerization

• Deletions/point mutations → constitutive activity

• Autocrine loops → cell produces ligand + receptor

• Fusion proteins → constitutive dimers

Cytokine receptors

Use JAK kinases, Immune/tumor signaling

TGF-β receptors

Ser/Thr kinase, Promotes tumor progression

Notch

Cleavage → NICD → transcription, T-cell leukemia

Hedgehog

Ptc/Smo/Gli pathway, Growth control in cancer

Wnt

Stabilizes β-catenin, Mutated in hereditary & sporadic cancers

GPCRs

Chemokines, cAMP, Tumor immunity modulation

Nuclear receptors

Steroid hormones, Breast, prostate, ovarian cancer

Integrins

ECM ligands, Anchorage-independent growth

Ras

• small GTPase “molecular switch.”

  • Normally cycles ON (GTP) / OFF (GDP).

  • Mutations block OFF switch → Ras always active → uncontrolled growth.

Integrins

• adhesion + signaling receptors.

  • Link ECM → cytoskeleton.

  • Required for survival (loss = apoptosis).

  • Cancer: reduced adhesion but selective integrins still vital.

Oncogenes disrupt…

normal growth factor signaling

common oncogenic tricks =

Autocrine loops, mutations, overexpression, fusion proteins

Ras mutations…

lock signaling “on,” mimicking constant growth factor stimulation

Therapies…

target these signaling errors.