Review Article

Caenorhabditis elegans: A Versatile In vivo Model for Decoding Conserved Oncogenic Signaling Pathways

DOI:

10.3791/72682

⸱

August 14th, 2026

 , 
1Institute of Pediatrics, Children's Hospital of Fudan University, 2Department of Rheumatology, The Second Affiliated Hospital of Jiaxing University

In This Article

Summary

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This review evaluates Caenorhabditis elegans as a complementary in vivo model for cancer-pathway research, focusing on conserved RTK-RAS-ERK, Notch, and Wnt signaling, representative mutants, quantitative readouts, genetic tools, anticancer screening, and chemosensation-based applications.

Abstract

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Caenorhabditis elegans (C. elegans) is a genetically tractable, transparent, and cost-effective metazoan model that bridges conventional cell-culture assays and mammalian systems for mechanistic cancer research. This pathway-focused review covers representative studies of conserved RAS/MAPK, Notch, and Wnt signaling and is organized around pathway conservation, mutant strains, quantitative phenotypes, genetic tools, and applications in mechanism studies, compound screening, and chemosensation-based assays. We first describe the conservation of pathway components and tumor-relevant phenotypes, including germline overproliferation and the multivulva (Muv) phenotype. We then catalog representative mutants, such as gain-of-function glp-1 and let-60 strains and loss-of-function gld-1 and lip-1 models, that enable analysis of stem-cell maintenance, ectopic proliferation, and signaling dysregulation. In addition, we discuss available tools for model construction, including RNA interference, transgenesis, MosTIC, TALENs, and CRISPR/Cas9, highlighting their strengths and limitations for cancer-related gene-function studies. Finally, we summarize published applications of C. elegans in anticancer drug screening, pathway discovery, and tumor-associated chemosensation. By integrating genetic conservation with scalable in vivo phenotyping, C. elegans provides a complementary platform for hypothesis generation, pathway validation, and early-stage therapeutic discovery, while its limitations in adaptive immunity and organ complexity should be recognized when translating findings to human cancer biology.

Introduction

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Cancer remains a leading cause of global morbidity and mortality. GLOBOCAN 2022 estimated close to 20 million new cancer cases and 9.7 million cancer deaths worldwide, including nonmelanoma skin cancers1. Because cancer incidence is projected to increase with population growth and aging2, experimental systems that can resolve conserved mechanisms and support efficient target prioritization remain essential.

Cancer mechanisms are commonly investigated in cultured cells and subsequently tested in vertebrate models. However, cell culture does not reproduce whole-organism physiology, whereas vertebrate studies are costly and comparatively low-throughput. A complementary model that combines genetic tractability, multicellular context, and rapid experimental turnaround can therefore bridge selected questions between in vitro assays and mammalian validation.

Caenorhabditis elegans (C. elegans) fills this complementary niche. At 20 °C, it develops from embryo to fertile adult in approximately 3 days, has a typical laboratory lifespan of 2–3 weeks, and produces about 300 self-progeny3. OrthoList 2 identified C. elegans orthologs for 10,678 of 20,310 human protein-coding genes (52.6%)4, whereas an earlier comparative proteomic analysis detected human homologs for approximately 83% of the C. elegans proteome5. In addition, approximately 72% of curated human cancer driver genes have at least one C. elegans ortholog6. Conserved processes include apoptosis, cell-cycle control, metabolism, stress responses, and RTK–RAS–ERK, Notch, Wnt, TGF-β, and insulin/IGF signaling3,4,6. Nevertheless, orthology does not imply complete functional equivalence, and the worm lacks vertebrate organs, adaptive immunity, angiogenesis, and a circulatory system6.

This review focuses on RTK (receptor tyrosine kinase)–RAS–ERK, Notch, and Wnt signaling because these pathways are evolutionarily conserved, frequently dysregulated in human cancer, and linked to readily scored C. elegans phenotypes. We distinguish true germline tumors from developmental hyperplasia or ectopic cell-fate phenotypes, summarize representative strains and quantitative readouts, review genetic tools for model construction, and discuss studies in which worm experiments clarified anticancer mechanisms or enabled compound prioritization.

Review and Perspective

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Conservation of oncogenic signaling pathways in C. elegans
Cancer is driven by combinations of genetic and epigenetic alterations that perturb proliferation, differentiation, survival, genome maintenance, metabolism, and interactions with the microenvironment. C. elegans cannot reproduce every feature of human malignancy, but it can isolate conserved pathway functions in a whole-animal context. The most informative models, therefore, pair a defined molecular lesion with a measurable phenotype and a clearly stated human-cancer analogy.

RTK-RAS-ERK signaling
Receptor tyrosine kinase (RTK) activation promotes receptor dimerization or rearrangement and trans-autophosphorylation of cytoplasmic tyrosine residues7. Phosphotyrosine docking sites recruit adaptor proteins and guanine nucleotide exchange factors, which convert RAS from the GDP-bound to the GTP-bound state7,8. RAS-GTP recruits RAF kinases to the plasma membrane, where RAF activation initiates the RAF–MEK–ERK kinase cascade8,9. Activated ERK phosphorylates cytoplasmic and nuclear substrates that regulate proliferation, differentiation, survival, and cell fate10. Oncogenic RAS mutations or aberrant RTK activity can therefore sustain pathway output independently of normal extracellular control8,11.

C. elegans encodes multiple RTKs, including LET-23/EGFR and EGL-15/FGFR12. During vulval induction, LIN-3/EGF activates LET-23 and the conserved SEM-5/GRB2–SOS-1–LET-60/RAS–LIN-45/RAF–MEK-2–MPK-1/ERK cascade12,13,14. ERK-dependent regulation of LIN-1 and LIN-31 determines vulval precursor-cell fates12,15. Reduced pathway activity produces a vulvaless phenotype, whereas excessive activation—such as gain-of-function let-60 alleles—produces the multivulva (Muv) phenotype15,16. The same pathway also regulates excretory duct development, uterine-vulval connections, and several male and germline processes12,17,18,19. EGL-15/FGFR signaling controls sex-myoblast migration, muscle maintenance, axon guidance, and fluid homeostasis20,21,22,23. Because pathway output is tissue- and stage-dependent, informative cancer-related models are defined by a specified molecular lesion, relevant tissue context, and quantitative readout12.

Notch signaling
Notch is a contact-dependent signaling pathway in which a membrane-bound Delta/Serrate/LAG-2 (DSL) ligand on one cell activates a Notch receptor on an adjacent cell24,25. During receptor maturation, an S1 cleavage occurs in the secretory pathway24. Ligand binding then exposes the S2 site to ADAM-family proteases, followed by S3 cleavage by γ-secretase24,25. The released Notch intracellular domain enters the nucleus and forms a transcriptional complex with CSL-family DNA-binding proteins and Mastermind-family coactivators24. In C. elegans, the corresponding nuclear factors are LAG-1 and SEL-825.

C. elegans has two Notch receptors, LIN-12 and GLP-125. In the adult germline, distal tip cells (DTCs) provide DSL ligands, principally LAG-2 and APX-1, to GLP-1 on adjacent germline stem/progenitor cells (GSCs)26,27. High GLP-1 activity maintains mitotic proliferation; as cells move away from the DTC, reduced Notch signaling permits the GLD pathways to promote meiotic entry28,29. Gain-of-function glp-1 alleles can maintain ectopic mitosis and produce germline tumors25,30. LIN-12 controls several somatic cell-fate decisions, including the anchor-cell/ventral-uterine decision; constitutive LIN-12 activity in vulval precursor cells produces a multivulva (Muv) phenotype, and activated GLP-1 can ectopically specify vulval fates25,31,32.

Proximal germline tumors can also arise through a non-cell-autonomous “latent niche” mechanism33. In pro-1 mutants or glp-1(ar202) gain-of-function mutants, delayed meiotic entry allows undifferentiated proximal germ cells to encounter DSL ligands, including APX-1 and ARG-1, from maturing gonadal sheath cells33. Continued GLP-1/Notch activation then sustains mitosis and tumor maintenance33. By contrast, loss of gld-1 causes germline tumors through failure of meiotic differentiation and should not be classified as direct activation of the Notch pathway34.

Wnt signaling
Wnt signaling regulates cell fate, polarity, migration, and proliferation through multiple context-dependent branches35,36. In the canonical β-catenin pathway, Wnt binding to Frizzled and LRP5/6 inhibits the AXIN–APC–GSK3–CK1 destruction complex, allowing β-catenin to accumulate and cooperate with TCF/LEF factors in the nucleus35,36. Dysregulation of this pathway is central to several human cancers, particularly colorectal cancer36.

C. elegans uses both a BAR-1/β-catenin canonical pathway and a divergent Wnt/β-catenin asymmetry pathway37,38. BAR-1-dependent signaling contributes to postembryonic cell-fate decisions, including vulval development37,38. In the asymmetry pathway, WRM-1/β-catenin and LIT-1/NLK reduce nuclear POP-1/TCF in one daughter cell, while SYS-1/β-catenin acts as a transcriptional coactivator; unequal POP-1 and SYS-1 levels generate distinct daughter-cell fates37,38,39. These worm-specific features differ from the mammalian canonical Wnt pathway and should be interpreted as distinct signaling architectures37,38.

Non-canonical Wnt signaling controls cell polarity and migration through Frizzled-dependent and receptor tyrosine kinase-like pathways35,40. In C. elegans, Wnt ligands and receptors guide neuronal and mesodermal migrations and orient asymmetric divisions37,41. These readouts are relevant to cancer biology because altered polarity and motility are prerequisites for invasion, although the worm does not model metastatic dissemination itself36,37.

Representative Wnt-pathway phenotypes include vulval-development defects in bar-1 loss-of-function animals42, embryonic polarity defects in mom-2 or mom-5 mutants37,43, and cell-migration or axon-guidance defects in mig-1 or prkl-1 mutants37,41. These strains are pathway-specific developmental models and are not direct equivalents of malignant tumors36,37.

Selection of cancer-relevant phenotypes and readouts
The term “tumor” should be used cautiously in C. elegans cancer-related models6. C. elegans germline tumors contain ectopically proliferating, differentiation-defective germ cells and therefore provide the closest worm analog of neoplastic overgrowth30,34,44. In contrast, the multivulva (Muv) phenotype reflects ectopic vulval cell-fate induction and tissue outgrowth; it is a sensitive readout of RAS/MAPK or Notch pathway activity but is not a malignant tumor15,16,25. In the distal germline, distal tip cell (DTC)-derived Notch signaling maintains the mitotic progenitor pool28,44. Gain-of-function glp-1 alleles or defects in meiotic differentiation genes such as gld-1 can expand mitotic germ cells30,34,44. In vulval precursor cells, let-60/RAS gain-of-function or reduced activity of negative regulators such as LIP-1 can produce or enhance Muv phenotypes15,16,45. These phenotype categories are summarized schematically in Figure 1. Figure 1A shows the normal anatomical context and baseline readouts used in C. elegans cancer-related assays. Figure 1D links LIN-3/LET-23-dependent RAS/MAPK signaling to vulval precursor-cell fate decisions, whereas Figure 1E illustrates GLP-1/Notch signaling in the distal germline stem-cell niche and latent-niche tumor mechanisms. Figure 1F further separates the BAR-1-dependent canonical Wnt branch from the Wnt/β-catenin asymmetry pathway, emphasizing that Wnt-related readouts in C. elegans should be interpreted as developmental or pathway-sensitive phenotypes rather than direct malignant-tumor models. Recommended quantitative endpoints include the percentage of Muv animals, number of ectopic vulval protrusions, mitotic-zone length, phospho-histone H3-positive germ cells, gonad area, fertility, reporter localization, and dose-response relationships15,28,30,44,45. Table 1 summarizes representative strains, their molecular lesions, phenotypes, quantitative assays, and cancer-related applications.

Genetic and experimental tools
C. elegans models can be generated by classical mutagenesis, transgenesis, RNA interference (RNAi), or targeted genome editing46,47,48. Gonadal microinjection efficiently creates extrachromosomal arrays46, whereas irradiation, microparticle bombardment, and single-copy insertion systems can generate integrated or low-copy transgenic lines and reduce copy-number and mosaicism artifacts47,48. Site-specific recombinases, Mos1-mediated single-copy insertion, zinc-finger nucleases, TALENs, and especially CRISPR/Cas9 enable targeted deletions, point mutations, endogenous tagging, conditional alleles, and humanized variants48,49. The method should be selected based on whether the study requires transient knockdown, stable loss, gain-of-function, tissue specificity, endogenous expression, or replacement with a human cancer variant48,49.

RNAi can be delivered by gonadal injection, soaking, or feeding bacteria that express double-stranded RNA50. It is rapid and scalable, but knockdown efficiency varies among tissues and genes, and RNAi produces a phenocopy rather than a defined heritable allele50. For compound studies, model validation should include genetic rescue or epistasis, independent alleles, and orthogonal readouts to distinguish pathway-specific effects from toxicity, developmental delay, or reduced food intake6,44.

The practical workflow for applying these models is summarized in Figure 2. In this framework, a cancer-related question is first mapped to a conserved signaling pathway and a defined molecular lesion, followed by selection of an appropriate C. elegans strain or engineered model, a quantitative phenotype, and validation controls. This stepwise design helps distinguish pathway-specific modulation from general toxicity or developmental delay and provides a rational basis for subsequent applications in mechanism studies, compound prioritization, or chemosensation-based assays.

Previous applications
Published studies illustrate how pathway-defined C. elegans models can support early-stage compound prioritization. In a mutation-specific EGFR platform, Bae et al. expressed LET-23 chimeric receptors containing the human EGFR tyrosine-kinase domain in vulval cells, including wild-type, L858R, and T790M/L858R variants. The activating L858R and T790M/L858R chimeras produced a multivulva (Muv) phenotype, enabling the percentage of Muv animals to serve as a quantitative screening endpoint. Gefitinib and erlotinib suppressed the L858R-associated Muv phenotype but not the T790M/L858R-associated phenotype. In a pilot screen of 8,960 small molecules, AG1478 and U0126 were identified as inhibitors of EGFR- or MEK-dependent signaling, respectively51. Medina et al. further evaluated the repurposing candidates itraconazole, disulfiram, etodolac, and ouabain in pathway-defined mutant strains representing Wnt, Notch, and RAS–ERK perturbations. Rescue of sterility, infertility, or Muv phenotypes was used as a phenotypic endpoint for compound prioritization52. More recently, Makhoul et al. tested EAPB02303 in MT2124 let-60(n1046gf) and MT4698 let-60(n1700gf) animals. They quantified both the proportion of animals displaying the Muv phenotype and the number of ectopic vulvae per animal and observed phenotypic suppression consistent with reduced LET-60/RAS–MAPK pathway activity. Their complementary lifespan and DAF-16 localization experiments also supported an effect on insulin/IGF-1–PI3K–AKT signaling53. Nevertheless, phenotypic rescue in these worm models should be interpreted as evidence of pathway modulation and early-stage compound prioritization, rather than direct proof of anticancer efficacy in mammalian tumors.

Germline tumor models distinguish mechanistically different routes from persistent proliferation. Gain-of-function glp-1 alleles sustain GLP-1/Notch-dependent mitosis in the germline, whereas pro-1 mutants reveal a non-cell-autonomous latent-niche mechanism in which proximal sheath-cell DSL ligands support aberrant mitotic maintenance. In contrast, gld-1 loss-of-function causes germline tumor formation primarily through defective meiotic differentiation rather than through direct activation of the Notch pathway. These models therefore provide complementary systems for studying stem-cell maintenance, differentiation failure, and microenvironment-dependent tumor initiation30,33,34.

Other cancer-related applications include LIN-35/Rb synthetic-lethal screens, CEP-1/p53-dependent apoptosis assays, and studies of AMPK and PI3K signaling6,44. Chemosensation-based applications should be considered separately from tumor modeling and drug screening. In these studies, C. elegans are exposed to cancer-associated volatile or urinary metabolites, and behavioral responses are measured as potential diagnostic signals. Such assays do not model tumor growth or anticancer drug activity and require analytical and clinical validation before diagnostic translation54,55.

Perspectives
C. elegans is most valuable when the biological question depends on conserved cell-autonomous or systemic mechanisms that can be tied to a quantitative phenotype. Its limitations—including absence of adaptive immunity, vasculature, organ-specific epithelia, and natural metastasis—preclude direct modeling of many tumor–stroma and immune interactions. Future opportunities include endogenous editing of patient-derived variants, tissue-specific perturbation, high-content imaging, automated phenotyping, and integration of worm genetics with human cancer genomics. Findings should be treated as mechanism- or target-generating evidence and validated in mammalian cells or vertebrate models before translational conclusions are drawn.

Conclusions

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C. elegans is a complementary, genetically tractable in vivo system for dissecting conserved cancer-related signaling and prioritizing candidate targets or compounds. Its most informative applications explicitly connect human cancer alterations to a conserved worm ortholog, tissue context, and quantitative phenotypes, such as germline overproliferation, multivulva formation, reporter activity, or drug response. Interpretation must distinguish true germline tumors from developmental pathway readouts and should be supported by independent alleles, genetic rescue or epistasis, and controls for toxicity and developmental delay. Although the worm cannot model adaptive immunity, vasculature, organ-specific architecture, or metastasis, it remains valuable for rapid hypothesis generation and early-stage pathway validation. Future work combining endogenous editing of patient-derived variants, tissue-specific perturbation, automated phenotyping, and cross-species validation will strengthen translation to mammalian cancer biology.

figure-results-1
Figure 1. Conserved cancer-related signaling readouts in C. elegans. (A) Wild-type anatomy and normal readouts. (B) Germline tumor-like overgrowth with expanded mitotic-zone readouts. (C) Multivulva (Muv) phenotype as a quantifiable pathway readout. (D) LIN-3/LET-23 RAS/MAPK signaling in vulval precursor cells. (E) GLP-1/Notch signaling in the germline stem-cell niche and latent-niche tumor mechanisms. (F) C. elegans Wnt branches are separated into the BAR-1-dependent canonical branch and the Wnt/β-catenin asymmetry pathway. Muv and Wnt-related phenotypes are developmental or pathway-sensitive readouts rather than direct models of malignant tumors. Please click here to view a larger version of this figure.

figure-results-2
Figure 2. Practical framework linking C. elegans models to cancer-related mechanisms and applications. The workflow links pathway selection, molecular-lesion definition, model-readout selection, quantitative validation, and cancer-related application. Representative uses include RAS/MAPK Muv suppression assays, germline tumor mechanism studies, pathway and toxicity controls, and non-tumor chemosensation-based applications. Please click here to view a larger version of this figure.

StrainGenotypeMolecular lesion / pathway branchPhenotype / readoutRecommended quantitative endpointRepresentative use / caution
CB1026lin-1(e1026) IV.RAS/MAPK transcriptional output; LIN-1 ETS repressor downstream of MPK-1/ERKMultivulva (Muv)% Muv animals; ectopic vulval protrusions/animalVulval RAS/MAPK output; developmental pathway readout, not malignant tumor
CB1275lin-1(e1275) IV.RAS/MAPK transcriptional outputMuv% Muv; protrusions/animalAlternative lin-1 allele for pathway-output confirmation
MT3516lin-1(e1275) cha-1(p1152) IV.RAS/MAPK output in a complex genetic backgroundMuv% Muv; developmental timing; fertilityUse with caution unless the cha-1 background is relevant to the assay
MT301lin-31(n301) II.RAS/MAPK-dependent transcriptional output; LIN-31 forkhead factorMuv% Muv; VPC fate-marker localizationVulval cell-fate readout downstream of LET-60/MPK-1
MT1001lin-1(e1777) IV.RAS/MAPK transcriptional outputMuv% Muv; protrusions/animalCorrected from Wnt to RAS/MAPK-related output
MT2124let-60(n1046gf) IV.LET-60/RAS gain of function; hyperactive RAS/MAPK signalingMuv% Muv; protrusions/animal; dose-response suppressionRAS/MAPK anticancer-compound screening and pathway suppression assays
MT4698let-60(n1700gf) IV.LET-60/RAS gain of function; hyperactive RAS/MAPK signalingMuv% Muv; protrusions/animal; dose-response suppressionRAS/MAPK compound-screening strain; used with MT2124 in EAPB02303 pathway-suppression studies
MT309lin-15B&lin-15A(n309) X.Synthetic multivulva; negative regulation of vulval induction/RAS-permissive backgroundMuv% Muv; penetrance; protrusions/animalModifier or sensitized Muv background; not a direct tumor model
ZM10942lin-15B&lin-15A(n765) X; hpIs774; hpEx4292.Synthetic Muv background with reporter/transgene contextMuv / reporter readout% Muv; reporter localization/intensityUse when reporter readout is essential; describe transgene/reporter in text
JK590glp-1(q35)/eT1 III; him-5(e1490)/eT1 V.GLP-1/Notch receptor C-terminal truncation; semi-dominant Muv with Glp phenotypeMuv sterile / Glp% Muv; sterility; progeny countsNotch-dependent vulval/germline developmental readout; do not group with distal germline tumor models
GC833glp-1(ar202) III.GLP-1/Notch gain of functionGermline tumorMitotic-zone length; pH3+ cells; gonad area; fertilityPersistent Notch-dependent mitosis in germline tumor model
BS3164unc-32(e189) glp-1(ar202) III.GLP-1/Notch gain of function with unc-32 marker/backgroundGermline tumorMitotic-zone length; pH3+ cells; gonad area; fertilityAlternative glp-1(ar202) background; state marker/background in methods
GC565pro-1(na48)/mIn1 [dpy-10(e128) mIs14] II.Latent-niche model; delayed meiotic entry permits proximal DSL ligand exposure and GLP-1/Notch activationProximal germline tumorProximal mitotic cells; pH3+ cells; gonad area; fertilityNon-cell-autonomous tumor initiation; distinguish from direct glp-1 gain of function
IT540gap-3(kp1) I; puf-8(zh17) unc-4(e120)/mnC1 [dpy-10(e128) unc-52(e444)] II.Mixed RAS/MAPK-associated and RNA-binding/differentiation backgroundMuv and germline tumor% Muv; mitotic-zone length; pH3+ cells; fertilityUse only with a clear mechanistic rationale because phenotypes arise from mixed pathways
XA774gld-1(q485)/gna-2(qa705) unc-55(e1170) I.GLD/meiotic differentiation failure; not direct Notch activationGermline tumorMitotic-zone length; pH3+ cells; gonad area; fertilityMeiotic differentiation-failure model; do not label as Notch
JK3025gld-1(q485) I/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III).GLD/meiotic differentiation failureGermline tumorMitotic-zone length; pH3+ cells; fertilityBalanced gld-1 tumor model; distinguish from glp-1/Notch tumors
JK1466gld-1(q485)/dpy-5(e61) unc-13(e51) I.GLD/meiotic differentiation failureGermline tumorMitotic-zone length; pH3+ cells; fertilityAlternative gld-1 background; distinguish from Notch-driven tumors
JK4299gld-2(q497) gld-1(q361) I/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III).GLD-1/GLD-2 meiotic-entry/differentiation pathwayGermline tumorMitotic-zone length; pH3+ cells; fertilityGLD pathway tumor model; not direct Notch activation
JK4832gld-1(q485) gld-2(q497) lst-1(ok814) sygl-1(tm5040) I/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III).GLD pathway plus stem-cell regulator backgroundGermline tumorMitotic-zone length; pH3+ cells; fertility; marker expressionMechanistically complex GLD/stem-cell fate model; state exact hypothesis
JK2879gld-2(q497) gld-1(q485)/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III).GLD-1/GLD-2 differentiation pathwayGermline tumorMitotic-zone length; pH3+ cells; fertilityAlternative balanced GLD-pathway tumor model
BS3156unc-13(e51) gld-1(q485)/hT2 [dpy-18(h662)] I; +/hT2 [bli-4(e937)] III.GLD/meiotic differentiation failure with marker/background mutationsGermline tumorMitotic-zone length; pH3+ cells; fertilityUse with genotype background clearly stated
JK5760lst-1(ok814) sygl-1(q828) gld-2(q497) gld-1(q361) I/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III).GLD pathway plus Notch target/stem-cell regulator backgroundGermline tumorMitotic-zone length; pH3+ cells; fertility; stem-cell marker expressionComplex germline stem-cell/differentiation model; do not collapse under “Notch”

Table 1: Representative C. elegans mutant strains and recommended cancer-related pathway readouts. Strain nomenclature and genotypes are based on CGC/WormBase records; pathway and phenotype annotations15,16,25,30,33,34,44,45,51,52,53. This table summarizes representative strains that illustrate commonly used pathway-specific readouts in cancer-related C. elegans studies.

Abbreviations: CGC, Caenorhabditis Genetics Center; DSL, Delta/Serrate/LAG-2-family ligand; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; gf, gain-of-function; GLD, germline development defective; Glp, germline proliferation-defective phenotype; lf, loss-of-function; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; Muv, multivulva; pH3+, phospho-histone H3-positive; RAS, rat sarcoma; RNAi, RNA interference; VPC, vulval precursor cell; Wnt, wingless/integrated. ETS, E26 transformation-specific.

Disclosures

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The authors declare no competing interests.

Acknowledgements

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We thank the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), for providing strain information and resources. This work was supported by the Zhejiang Provincial Health Bureau Science Foundation (No. 2025KY1608).

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Cancer ResearchCaenorhabditis eleganscancer modelcancer signalgermline tumorMulti vulval

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