Wnt Signaling Tournament
Two onboarding diagrams orient you in the Wnt pathway. Then eight MCAT-DoK quiz rounds: destruction complex (APC + Axin + GSK3β + CK1α), Wnt -> Frizzled / LRP5/6 -> Dvl, β-catenin nuclear translocation, TCF/LEF target genes (c-Myc, cyclin D1, LGR5), APC loss in FAP / colon cancer, and DKK / sclerostin in bone biology.
Where the Signaling by Wnt fits in Signal Transduction
Wnt signaling is one of the eight major Reactome 'Signal Transduction' branches and a master controller of stem-cell maintenance and developmental patterning. The canonical pathway acts through β-catenin stabilization. Click the highlighted Wnt box to enter the tournament.
Click the highlighted Signaling by Wnt box to continue.
What this tournament tests
Each task maps to a distinct MCAT cognitive demand. The first two orient you in the broader topology; the next eight test the high-yield mechanism, regulation, sequence and quantitative reasoning that consistently appear on test day.
The Bigger Picture
Anchor Wnt signaling within the Reactome Signal Transduction overview alongside Hedgehog and Notch developmental pathways.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways Wnt pathway figure before answering questions.
Fill in the Blank
Recall that GSK3β is the kinase of the β-catenin destruction complex.
APC / Colon Cancer Disruptor
Predict why APC loss drives colon cancer through unrestrained β-catenin.
Sequence Ordering
Order Wnt -> Frizzled / LRP5/6 -> Dvl -> destruction complex disassembly -> β-catenin nuclear translocation -> TCF/LEF activation.
Match the Pairs
Pair Frizzled, LRP5/6, Dvl, APC, Axin, β-catenin, TCF/LEF, and DKK with their precise pathway roles.
Numeric Input
Count the transmembrane domains of Frizzled (7TM).
Select All That Apply
Identify true statements about canonical Wnt, non-canonical Wnt-Ca2+, and the dual role of β-catenin in adherens junctions.
Odd One Out
Distinguish destruction complex components from β-catenin (the substrate).
Bone Biology Disruptor
Predict why romosozumab (anti-sclerostin) increases bone density via Wnt activation in osteoblasts.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
Wnt signaling in 60 seconds
In the absence of Wnt, the destruction complex (APC + Axin + GSK3β + CK1α) phosphorylates β-catenin, which is then ubiquitinated by βTrCP and degraded by the proteasome. Cytoplasmic β-catenin levels stay low and the pathway is OFF.
Wnt ligand binds Frizzled (7TM) and LRP5/6 (single-pass co-receptor). The receptors recruit Dishevelled (Dvl), which sequesters Axin and dismantles the destruction complex. β-catenin escapes phosphorylation and degradation.
Stabilized β-catenin enters the nucleus, binds TCF / LEF, and activates Wnt target genes - c-Myc, cyclin D1, LGR5, Axin2. Functionally, Wnt promotes proliferation, stem-cell self-renewal, and developmental patterning.
Pathology: APC loss -> familial adenomatous polyposis (FAP) and ~85% of sporadic colorectal cancers. Bone biology: sclerostin and DKK1 are secreted Wnt antagonists - romosozumab (anti-sclerostin) is FDA-approved for osteoporosis.
FAQ
Why is APC such a powerful colorectal cancer driver?
Intestinal epithelium turns over rapidly and is exquisitely Wnt-dependent (LGR5+ crypt stem cells need Wnt to self-renew). APC loss makes Wnt signaling constitutive, so every cell in the proliferative compartment behaves like a stem cell. The Knudson 'two-hit' model applies: germline APC mutation in FAP + somatic loss of the wild-type allele in each polyp.
What is non-canonical Wnt signaling?
Two flavors: Wnt-PCP (planar cell polarity) uses Dvl + small Rho-family GTPases + JNK to organize cytoskeleton and tissue polarity. Wnt-Ca2+ uses Gαq -> PLC -> IP3 + DAG + Ca2+. Neither requires β-catenin. Non-canonical Wnt is essential for convergent extension during gastrulation, hair-cell polarity in the inner ear, and various developmental morphogenesis events.
Why is β-catenin a 'moonlighting' protein?
β-catenin has TWO completely distinct roles: (1) at adherens junctions it links E-cadherin to α-catenin and the actin cytoskeleton; (2) in the nucleus it acts as a transcriptional coactivator with TCF/LEF. The cell uses post-translational modification + subcellular localization to switch between these roles. Loss of E-cadherin can liberate β-catenin and contribute to epithelial-mesenchymal transition in cancer.
Do I need an account to play?
No. The tournament is fully public. You get a randomized handle and your score posts to the public leaderboard at the bottom of this page.
Keep going
Another developmental signaling pathway: Patched / Smoothened / GLI and basal cell carcinoma.
Developmental signaling via regulated intramembrane proteolysis - cell-cell juxtacrine logic.
Overview diagram: Reactome Pathway R-HSA-162582, licensed CC BY 4.0.