Dong, M. et al. Sex differences in cancer incidence and survival: a pan-cancer analysis. Cancer Epidemiol. Biomarkers Prev. 29, 1389–1397 (2020).
Ye, Y. et al. Sex-associated molecular differences for cancer immunotherapy. Nat. Commun. 11, 1779 (2020).
Vellano, C. P. et al. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy. Nature 606, 797–803 (2022).
Zhao, Y., Wang, X., Liu, Y., Wang, H.-Y. & Xiang, J. The effects of estrogen on targeted cancer therapy drugs. Pharmacol. Res. 177, 106131 (2022).
Rubin, J. B. et al. Sex differences in cancer mechanisms. Biol. Sex Differ. 11, 17 (2020).
Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).
Cook, M. B. et al. Sex disparities in cancer incidence by period and age. Cancer Epidemiol. Biomarkers Prev. 18, 1174–1182 (2009).
Metcalfe, A. et al. Incidence of pregnancy-associated cancer in two Canadian provinces: a population-based study. Int. J. Environ. Res. Public Health 18, 3100 (2021).
Lee, Y. Y. et al. Incidence and outcomes of pregnancy-associated cancer in Australia, 1994–2008: a population-based linkage study. BJOG 119, 1572–1582 (2012).
Benyi, E. et al. Risks of malignant and non-malignant tumours in tall women treated with high-dose oestrogen during adolescence. Horm. Res. Paediatr. 82, 89–96 (2014).
Ackermann, J. et al. Metastasizing melanoma formation caused by expression of activated N-RasQ61K on an INK4a-deficient background. Cancer Res. 65, 4005–4011 (2005).
Raymond, J. H., Aktary, Z., Larue, L. & Delmas, V. Targeting GPCRs and their signaling as a therapeutic option in melanoma. Cancers 14, 706 (2022).
Farshidfar, F. et al. Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis. Nat. Commun. 13, 898 (2022).
Yu, F.-X. et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25, 822–830 (2014).
Verfaillie, A. et al. Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state. Nat. Commun. 6, 6683 (2015).
Zhang, X. et al. The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis. Oncogene 39, 5267–5281 (2020).
Zhao, B. et al. YAP activation in melanoma contributes to anoikis resistance and metastasis. Exp. Biol. Med. (Maywood) 246, 888–896 (2021).
Sommer, S. & Fuqua, S. A. Estrogen receptor and breast cancer. Semin. Cancer Biol. 11, 339–352 (2001).
Berx, G. & Van Roy, F. The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res. 3, 289–293 (2001).
Guilford, P. et al. E-cadherin germline mutations in familial gastric cancer. Nature 392, 402–405 (1998).
Uhlén, M. et al. Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (2015).
Cano, A. et al. The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol. 2, 76–83 (2000).
Venza, M. et al. DNA methylation-induced E-cadherin silencing is correlated with the clinicopathological features of melanoma. Oncol. Rep. 35, 2451–2460 (2016).
Larue, L. & Delmas, V. The WNT/Beta-catenin pathway in melanoma. Front. Biosci. 11, 733–742 (2006).
Avberšek, M., Žegura, B., Filipič, M., Uranjek-Ževart, N. & Heath, E. Determination of estrogenic potential in waste water without sample extraction. J. Hazard. Mater. 260, 527–533 (2013).
Robinson, D. R. et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat. Genet. 45, 1446–1451 (2013).
Liu, X.-Y. et al. Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell 147, 447–458 (2011).
Herzig, M., Savarese, F., Novatchkova, M., Semb, H. & Christofori, G. Tumor progression induced by the loss of E-cadherin independent of β-catenin/Tcf-mediated Wnt signaling. Oncogene 26, 2290–2298 (2007).
Jeanes, A., Gottardi, C. J. & Yap, A. S. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27, 6920–6929 (2008).
Larue, L. et al. A role for cadherins in tissue formation. Development 122, 3185–3194 (1996).
Morali, O. G. et al. IGF-II induces rapid β-catenin relocation to the nucleus during epithelium to mesenchyme transition. Oncogene 20, 4942–4950 (2001).
Qian, X., Karpova, T., Sheppard, A. M., McNally, J. & Lowy, D. R. E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. EMBO J. 23, 1739–1748 (2004).
Elangovan, A. et al. Loss of E-cadherin induces IGF1R activation and reveals a targetable pathway in invasive lobular breast carcinoma. Mol. Cancer Res. 20, 1405–1419 (2022).
Johnson, K. S. et al. CTCF expression and dynamic motif accessibility modulates epithelial-mesenchymal gene expression. Cancers 14, 209 (2022).
Centore, R. C., Sandoval, G. J., Soares, L. M. M., Kadoch, C. & Chan, H. M. Mammalian SWI/SNF chromatin remodeling complexes: emerging mechanisms and therapeutic strategies. Trends Genet. 36, 936–950 (2020).
Hsiao, P.-W., Fryer, C. J., Trotter, K. W., Wang, W. & Archer, T. K. BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Mol. Cell. Biol. 23, 6210–6220 (2003).
Emons, G. Hormone-dependent cancers: molecular mechanisms and therapeutical implications. Cells 12, 110 (2022).
Rižner, T. L. & Romano, A. Targeting the formation of estrogens for treatment of hormone dependent diseases–current status. Front. Pharmacol. 14, 1155558 (2023).
Saeki, A., Yamanaka, H., Kobayashi, K., Okubo, M. & Noguchi, K. Analgesic effect of gastrin-releasing peptide in the dorsal horn. Mol. Pain 18, 17448069221108965 (2022).
Polgár, E. et al. Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain. Pain 164, 149–170 (2023).
Patel, O., Shulkes, A. & Baldwin, G. S. Gastrin-releasing peptide and cancer. Biochim. Biophys. Acta 1766, 23–41 (2006).
Schwartsmann, G. et al. A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies. Invest. New Drugs 24, 403–412 (2006).
Hampton, L. L. et al. Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice. Proc. Natl Acad. Sci. USA 95, 3188–3192 (1998).
Chen, Z.-F. A neuropeptide code for itch. Nat. Rev. Neurosci. 22, 758–776 (2021).
Peng, S. et al. Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy. Proc. Natl Acad. Sci. USA 120, e2216230120 (2023).
Li, C. et al. Molecular recognition of itch-associated neuropeptides by bombesin receptors. Cell Res. 33, 184–187 (2023).
Pobbati, A. V. & Hong, W. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics 10, 3622–3635 (2020).
He, Z., Li, R. & Jiang, H. Mutations and copy number abnormalities of Hippo pathway components in human cancers. Front. Cell Dev. Biol. 9, 661718 (2021).
Mills, K. R., Misra, J. & Torabifard, H. Allosteric modulation of the YAP/TAZ-TEAD interaction by palmitoylation and small-molecule inhibitors. J. Phys. Chem. B 128, 3795–3806 (2024).
Deltourbe, L. G. et al. Steroid hormone levels vary with sex, aging, lifestyle, and genetic. Sci. Adv. 11, eadu6094 (2025).
Colaprico, A. et al. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 44, e71 (2016).
Rambow, F. et al. Toward minimal residual disease-directed therapy in melanoma. Cell 174, 843–855 (2018).
Maag, J. L. V. gganatogram: An R package for modular visualisation of anatograms and tissues based on ggplot2. F1000Research https://doi.org/10.12688/f1000research.16409.2 (2018).
Delmas, V. et al. β-Catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev. 21, 2923–2935 (2007).
Boussadia, O., Kutsch, S., Hierholzer, A., Delmas, V. & Kemler, R. E-cadherin is a survival factor for the lactating mouse mammary gland. Mech. Dev. 115, 53–62 (2002).
Delmas, V., Martinozzi, S., Bourgeois, Y., Holzenberger, M. & Larue, L. Cre-mediated recombination in the skin melanocyte lineage. Genesis 36, 73–80 (2003).
Serrano, M. et al. Role of the INK4a locus in tumor suppression and cell mortality. Cell 85, 27–37 (1996).
Lesche, R. et al. Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32, 148–149 (2002).
Hamm, M. et al. BRN2 is a non-canonical melanoma tumor-suppressor. Nat. Commun. 12, 3707 (2021).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E. & Storey, J. D. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28, 882–883 (2012).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2016).
Petit, V. et al. C57BL/6 congenic mouse NRASQ61K melanoma cell lines are highly sensitive to the combination of Mek and Akt inhibitors in vitro and in vivo. Pigment Cell Melanoma Res. 32, 829–841 (2019).
Cailleau, R., Olivé, M. & Cruciger, Q. V. Long-term human breast carcinoma cell lines of metastatic origin: preliminary characterization. In Vitro 14, 911–915 (1978).
Marincola, F. M. et al. Loss of HLA haplotype and B locus down-regulation in melanoma cell lines. J. Immunol. 153, 1225–1237 (1994).
Rambow, F. et al. New functional signatures for understanding melanoma biology from tumor cell lineage-specific analysis. Cell Rep. 13, 840–853 (2015).
Soule, H. D., Vazguez, J., Long, A., Albert, S. & Brennan, M. A human cell line from a pleural effusion derived from a breast carcinoma. J. Natl Cancer Inst. 51, 1409–1416 (1973).
Chirumamilla, C. S. et al. Profiling activity of cellular kinases in migrating T-cells. Methods Mol. Biol. 1930, 99–113 (2019).
Johnson, W. E., Li, C. & Rabinovic, A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8, 118–127 (2007).
Motakis, E. S., Nason, G. P., Fryzlewicz, P. & Rutter, G. A. Variance stabilization and normalization for one-color microarray data using a data-driven multiscale approach. Bioinformatics 22, 2547–2553 (2006).
The Galaxy Community. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2022 update. Nucleic Acids Res. 50, W345–W351 (2022).
Langmead, B., Wilks, C., Antonescu, V. & Charles, R. Scaling read aligners to hundreds of threads on general-purpose processors. Bioinformatics 35, 421–432 (2019).
Hewitt, S. C. et al. Research resource: whole-genome estrogen receptor α binding in mouse uterine tissue revealed by ChIP-seq. Mol. Endocrinol. 26, 887–898 (2012).
Park, J.-S. et al. Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev. Cell 23, 637–651 (2012).
Rhie, S. K. et al. Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits. Epigenetics Chromatin 9, 50 (2016).
Nair, S. J. et al. Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nat. Struct. Mol. Biol. 26, 193–203 (2019).
Ross-Innes, C. S. et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 481, 389–393 (2012).
Estarás, C., Benner, C. & Jones, K. A. SMADs and YAP compete to control elongation of β-catenin:LEF-1-recruited RNAPII during hESC differentiation. Mol. Cell 58, 780–793 (2015).
Perovanovic, J. et al. Oct1 cooperates with the Smad family of transcription factors to promote mesodermal lineage specification. Sci. Signal. 16, eadd5750 (2023).
Luo, Y. et al. New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Res. 48, D882–D889 (2020).
Dixon, J. R. et al. Chromatin architecture reorganization during stem cell differentiation. Nature 518, 331–336 (2015).
Yu, G., Wang, L.-G. & He, Q.-Y. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382–2383 (2015).
