The nature of cancer

References

[1] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674

[2] Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov 2022; 12(1): 31–46

[3] Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol 2019; 29(3): 212–226

[4] Arozarena I, Wellbrock C. Phenotype plasticity as enabler of melanoma progression and therapy resistance. Nat Rev Cancer 2019; 19(7): 377–391

[5] Kurppa KJ, Liu Y, To C, Zhang T, Fan M, Vajdi A, Knelson EH, Xie Y, Lim K, Cejas P, Portell A, Lizotte PH, Ficarro SB, Li S, Chen T, Haikala HM, Wang H, Bahcall M, Gao Y, Shalhout S, Boettcher S, Shin BH, Thai T, Wilkens MK, Tillgren ML, Mushajiang M, Xu M, Choi J, Bertram AA, Ebert BL, Beroukhim R, Bandopadhayay P, Awad MM, Gokhale PC, Kirschmeier PT, Marto JA, Camargo FD, Haq R, Paweletz CP, Wong KK, Barbie DA, Long HW, Gray NS, Jänne PA. Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway. Cancer Cell 2020; 37(1): 104–122.e12

[6] Milanovic M, Yu Y, Schmitt CA. The senescence-stemness alliance—a cancer-hijacked regeneration principle. Trends Cell Biol 2018; 28(12): 1049–1061

[7] Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, Dörr JR, Dimitrova L, Lenze D, Monteiro Barbosa IA, Mendoza-Parra MA, Kanashova T, Metzner M, Pardon K, Reimann M, Trumpp A, Dörken B, Zuber J, Gronemeyer H, Hummel M, Dittmar G, Lee S, Schmitt CA. Senescence-associated reprogramming promotes cancer stemness. Nature 2018; 553(7686): 96–100

[8] Li F, Han X, Li F, Wang R, Wang H, Gao Y, Wang X, Fang Z, Zhang W, Yao S, Tong X, Wang Y, Feng Y, Sun Y, Li Y, Wong KK, Zhai Q, Chen H, Ji H. LKB1 inactivation elicits a Redox imbalance to modulate non-small cell lung cancer plasticity and therapeutic response. Cancer Cell 2015; 27(5): 698–711

[9] Zhang H, Fillmore Brainson C, Koyama S, Redig AJ, Chen T, Li S, Gupta M, Garcia-de-Alba C, Paschini M, Herter-Sprie GS, Lu G, Zhang X, Marsh BP, Tuminello SJ, Xu C, Chen Z, Wang X, Akbay EA, Zheng M, Palakurthi S, Sholl LM, Rustgi AK, Kwiatkowski DJ, Diehl JA, Bass AJ, Sharpless NE, Dranoff G, Hammerman PS, Ji H, Bardeesy N, Saur D, Watanabe H, Kim CF, Wong KK. Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2. Nat Commun 2017; 8: 14922

[10] Quintanal-Villalonga Á, Chan JM, Yu HA, Pe’er D, Sawyers CL, Sen T, Rudin CM. Lineage plasticity in cancer: a shared pathway of therapeutic resistance. Nat Rev Clin Oncol 2020; 17(6): 360–371

[11] Biehs B, Dijkgraaf GJP, Piskol R, Alicke B, Boumahdi S, Peale F, Gould SE, de Sauvage FJ. A cell identity switch allows residual BCC to survive Hedgehog pathway inhibition. Nature 2018; 562(7727): 429–433

[12] Venkataramani V, Tanev DI, Strahle C, Studier-Fischer A, Fankhauser L, Kessler T, Körber C, Kardorff M, Ratliff M, Xie R, Horstmann H, Messer M, Paik SP, Knabbe J, Sahm F, Kurz FT, Acikgöz AA, Herrmannsdörfer F, Agarwal A, Bergles DE, Chalmers A, Miletic H, Turcan S, Mawrin C, Hänggi D, Liu HK, Wick W, Winkler F, Kuner T. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 2019; 573(7775): 532–538

[13] Zeng Q, Michael IP, Zhang P, Saghafinia S, Knott G, Jiao W, McCabe BD, Galván JA, Robinson HPC, Zlobec I, Ciriello G, Hanahan D. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature 2019; 573(7775): 526–531

[14] Pastushenko I, Mauri F, Song Y, de Cock F, Meeusen B, Swedlund B, Impens F, Van Haver D, Opitz M, Thery M, Bareche Y, Lapouge G, Vermeersch M, Van Eycke YR, Balsat C, Decaestecker C, Sokolow Y, Hassid S, Perez-Bustillo A, Agreda-Moreno B, Rios-Buceta L, Jaen P, Redondo P, Sieira-Gil R, Millan-Cayetano JF, Sanmatrtin O, D’Haene N, Moers V, Rozzi M, Blondeau J, Lemaire S, Scozzaro S, Janssens V, De Troya M, Dubois C, Pérez-Morga D, Salmon I, Sotiriou C, Helmbacher F, Blanpain C. Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis. Nature 2021; 589(7842): 448–455

[15] Gulati GS, Sikandar SS, Wesche DJ, Manjunath A, Bharadwaj A, Berger MJ, Ilagan F, Kuo AH, Hsieh RW, Cai S, Zabala M, Scheeren FA, Lobo NA, Qian D, Yu FB, Dirbas FM, Clarke MF, Newman AM. Single-cell transcriptional diversity is a hallmark of developmental potential. Science 2020; 367(6476): 405–411

[16] Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, Reinhardt F, D’Alessio AC, Young RA, Weinberg RA. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 2013; 154(1): 61–74

[17] Dupuy F, Tabariès S, Andrzejewski S, Dong Z, Blagih J, Annis MG, Omeroglu A, Gao D, Leung S, Amir E, Clemons M, Aguilar-Mahecha A, Basik M, Vincent EE, St-Pierre J, Jones RG, Siegel PM. PDK1-dependent metabolic reprogramming dictates metastatic potential in breast cancer. Cell Metab 2015; 22(4): 577–589

[18] Venkataramani V, Yang Y, Schubert MC, Reyhan E, Tetzlaff SK, Wißmann N, Botz M, Soyka SJ, Beretta CA, Pramatarov RL, Fankhauser L, Garofano L, Freudenberg A, Wagner J, Tanev DI, Ratliff M, Xie R, Kessler T, Hoffmann DC, Hai L, Dörflinger Y, Hoppe S, Yabo YA, Golebiewska A, Niclou SP, Sahm F, Lasorella A, Slowik M, Döring L, Iavarone A, Wick W, Kuner T, Winkler F. Glioblastoma hijacks neuronal mechanisms for brain invasion. Cell 2022; 185(16): 2899–2917.e31

[19] Georgouli M, Herraiz C, Crosas-Molist E, Fanshawe B, Maiques O, Perdrix A, Pandya P, Rodriguez-Hernandez I, Ilieva KM, Cantelli G, Karagiannis P, Mele S, Lam H, Josephs DH, Matias-Guiu X, Marti RM, Nestle FO, Orgaz JL, Malanchi I, Fruhwirth GO, Karagiannis SN, Sanz-Moreno V. Regional activation of myosin II in cancer cells drives tumor progression via a secretory cross-talk with the immune microenvironment. Cell 2019; 176(4): 757–774.e23

[20] Zahalka AH, Frenette PS. Nerves in cancer. Nat Rev Cancer 2020; 20(3): 143–157

[21] Lu R, Fan C, Shangguan W, Liu Y, Li Y, Shang Y, Yin D, Zhang S, Huang Q, Li X, Meng W, Xu H, Zhou Z, Hu J, Li W, Liu L, Mo X. Neurons generated from carcinoma stem cells support cancer progression. Signal Transduct Target Ther 2017; 2(1): 16036

[22] Aiello NM, Kang Y. Context-dependent EMT programs in cancer metastasis. J Exp Med 2019; 216(5): 1016–1026

[23] Ji AL, Rubin AJ, Thrane K, Jiang S, Reynolds DL, Meyers RM, Guo MG, George BM, Mollbrink A, Bergenstråhle J, Larsson L, Bai Y, Zhu B, Bhaduri A, Meyers JM, Rovira-Clavé X, Hollmig ST, Aasi SZ, Nolan GP, Lundeberg J, Khavari PA. Multimodal analysis of composition and spatial architecture in human squamous cell carcinoma. Cell 2020; 182(2): 497–514.e22

[24] Yan W, Wu X, Zhou W, Fong MY, Cao M, Liu J, Liu X, Chen CH, Fadare O, Pizzo DP, Wu J, Liu L, Liu X, Chin AR, Ren X, Chen Y, Locasale JW, Wang SE. Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nat Cell Biol 2018; 20(5): 597–609

[25] Cleary AS, Leonard TL, Gestl SA, Gunther EJ. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers. Nature 2014; 508(7494): 113–117

[26] Polyak K, Marusyk A. Cancer: clonal cooperation. Nature 2014; 508(7494): 52–53

[27] Seton-Rogers S. Tumour heterogeneity: a cooperative tumour cell community. Nat Rev Cancer 2014; 14(5): 294

[28] McGranahan N, Swanton C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 2015; 27(1): 15–26

[29] McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 2017; 168(4): 613–628

[30] Hiley C, de Bruin EC, McGranahan N, Swanton C. Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine. Genome Biol 2014; 15(8): 453

[31] Cipponi A, Goode DL, Bedo J, McCabe MJ, Pajic M, Croucher DR, Rajal AG, Junankar SR, Saunders DN, Lobachevsky P, Papenfuss AT, Nessem D, Nobis M, Warren SC, Timpson P, Cowley M, Vargas AC, Qiu MR, Generali DG, Keerthikumar S, Nguyen U, Corcoran NM, Long GV, Blay JY, Thomas DM. MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer. Science 2020; 368(6495): 1127–1131

[32] Chen X, Song E. The theory of tumor ecosystem. Cancer Commun (Lond) 2022; 42(7): 587–608

[33] Mueller S, Engleitner T, Maresch R, Zukowska M, Lange S, Kaltenbacher T, Konukiewitz B, Öllinger R, Zwiebel M, Strong A, Yen HY, Banerjee R, Louzada S, Fu B, Seidler B, Götzfried J, Schuck K, Hassan Z, Arbeiter A, Schönhuber N, Klein S, Veltkamp C, Friedrich M, Rad L, Barenboim M, Ziegenhain C, Hess J, Dovey OM, Eser S, Parekh S, Constantino-Casas F, de la Rosa J, Sierra MI, Fraga M, Mayerle J, Klöppel G, Cadiñanos J, Liu P, Vassiliou G, Weichert W, Steiger K, Enard W, Schmid RM, Yang F, Unger K, Schneider G, Varela I, Bradley A, Saur D, Rad R. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. Nature 2018; 554(7690): 62–68

[34] Van Keymeulen A, Lee MY, Ousset M, Brohée S, Rorive S, Giraddi RR, Wuidart A, Bouvencourt G, Dubois C, Salmon I, Sotiriou C, Phillips WA, Blanpain C. Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity. Nature 2015; 525(7567): 119–123

[35] Koren S, Reavie L, Couto JP, De Silva D, Stadler MB, Roloff T, Britschgi A, Eichlisberger T, Kohler H, Aina O, Cardiff RD, Bentires-Alj M. PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours. Nature 2015; 525(7567): 114–118

[36] Cui B, Peng F, Lu J, He B, Su Q, Luo H, Deng Z, Jiang T, Su K, Huang Y, Ud Din Z, Lam EW, Kelley KW, Liu Q. Cancer and stress: NextGen strategies. Brain Behav Immun 2021; 93: 368–383

[37] Reiche EMV, Nunes SOV, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol 2004; 5(10): 617–625

[38] Powell ND, Tarr AJ, Sheridan JF. Psychosocial stress and inflammation in cancer. Brain Behav Immun 2013; 30(Suppl): S41–S47

[39] Schneider MA, Heeb L, Beffinger MM, Pantelyushin S, Linecker M, Roth L, Lehmann K, Ungethüm U, Kobold S, Graf R, van den Broek M, Vom Berg J, Gupta A, Clavien PA. Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models. Sci Transl Med 2021; 13(611): eabc8188

[40] Carlino MS, Larkin J, Long GV. Immune checkpoint inhibitors in melanoma. Lancet 2021; 398(10304): 1002–1014

Acknowledgements

We thank Prof. Eric W.-F. Lam, Prof. Keith W. Kelley, and all members of Liu laboratory for their critical comments and manuscript editing. This work was supported by the National Key Research and Development Program of China (No. 2019YFA0110303 to Quentin Liu), the National Natural Science Foundation of China (No. 81972594 to Min Yan), the Innovative Research Team in University of Ministry of Education of China (No. IRT-17R15 to Quentin Liu), the Natural Science Foundation of Guangdong (No. 2020A1515010608 to Min Yan).

Compliance with ethics guidelines

Min Yan and Quentin Liu have no potential conflicts of interest to disclose. This manuscript is a perspective and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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