Asymmetric Cell Division as a Mechanistic Contributor to Cancer with a Focus on Glioblastoma

Abstract

Asymmetric cell division (ACD) has a crucial role in normal cellular differentiation and tissue homeostasis. The mechanisms underlying ACD are highly intricate and involve coordinated molecular and cellular processes. Dysregulation of ACD has been implicated in various human cancers by contributing to malignant tumor initiation, progression, metastasis, and treatment resistance. Although numerous studies have explored the relationship between ACD and cancer, many questions remain unanswered. This literature review aims to evaluate the potential biological significance of ACD in cancer with a focus on the diagnostic and prognostic relevance to glioblastoma. A comprehensive PubMed search was conducted from 2008 to the present using keywords, such as “asymmetric cell division”, “cancer”, “glioblastoma”, and “tumorigenesis”. The selected articles were analyzed to assess ACD-related data and the clinical correlations. Special emphasis was placed on glioblastomas, an aggressive brain tumor with limited improvement in patient survival over recent years. The review underscores the crucial role of ACD in normal tissue homeostasis and ACD dysregulation in cancer initiation, progression, therapeutic resistance, and metastatic potential. Understanding how ACD contributes to cancer heterogeneity may provide insights into innovative strategies for tumor detection, monitoring, and treatment. Future research into the molecular mechanisms governing ACD could facilitate the development of novel glioblastoma therapies aimed at restoring or modulating ACD processes to improve patient outcomes.

Keywords

Asymmetric cell division / cancer / glioblastoma / tumorigenesis

References

[1] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74. [PMID: 21376230 DOI: 10.1016/j.cell.2011.02.013]

[2] Chen R, Smith-Cohn M, Cohen AL, Colman H. Glioma subclassifications and their clinical significance. Neurotherapeutics 2017; 14(2): 284-97. [PMID: 28281173 DOI: 10.1007/s13311-017-0519-x]

[3] Wang LM, Englander ZK, Miller ML, Bruce JN. Malignant glioma. Adv Exp Med Biol 2023; 1405: 1-30. [PMID: 37452933 DOI: 10.1007/978-3-031-23705-8_1]

[4] Liu H, Hamaia SW, Dobson L, Weng J, Hernández FL, Beaudoin CA, et al. The voltage-gated sodium channel β3 subunit modulates C6 glioma cell motility independently of channel activity. Biochim Biophys Acta Mol Basis Dis 2025; 1871(16): 167844. [PMID: 40245999 DOI: 10.1016/j.bbadis.2025.167844]

[5] Hitomi M, Chumakova AP, Silver DJ, Knudsen AM, Pontius WD, Murphy S, et al. Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells. JCI Insight 2021; 6(3): e130510. [PMID: 33351787 DOI: 10.1172/jci.insight.130510]

[6] Deng W, Lin H. Spectrosomes and fusomes anchor mitotic spindles during asymmetric germ cell divisions and facilitate the formation of a polarized microtubule array for oocyte specification in Drosophila. Dev Biol 1997; 189(1): 79-94. [PMID: 9281339 DOI: 10.1006/dbio.1997.8669]

[7] Daynac M, Petritsch CK. Regulation of asymmetric cell division in mammalian neural stem and cancer precursor cells. Results Probl Cell Differ 2017; 61: 375-99. [PMID: 28409314 DOI: 10.1007/978-3-319-53150-2_17]

[8] Samanta P, Bhowmik A, Biswas S, Sarkar R, Ghosh R, Pakhira S, et al. Therapeutic effectiveness of anticancer agents targeting different signaling molecules involved in asymmetric division of cancer stem cell. Stem Cell Rev Rep 2023; 19(5): 1283-306. [PMID: 36952080 DOI: 10.1007/s12015-023-10523-3]

[9] Wei M, Nurjanah U, Li J, Luo X, Hosea R, Li Y, et al. YY2-DRP1 axis regulates mitochondrial fission and determines cancer stem cell asymmetric division. Adv Sci 2023; 10(23): e2207349. [PMID: 37300334 DOI: 10.1002/advs.202207349]

[10] Tamori S, Matsuda C, Kasai T, Ohno S, Sasaki K, Akimoto K. Asymmetric cell division of ALDH1-positive cancer stem cells generates glycolytic metabolically diverse cell populations. Sci Rep 2025; 15(1): 13932. [PMID: 40263471 DOI: 10.1038/s41598-025-97985-2]

[11] Gonzalez C. Centrosomes in asymmetric cell division. Curr Opin Struct Biol 2021; 66: 178-82. [PMID: 33279730 DOI: 10.1016/j.sbi.2020.10.023]

[12] Chen C, Yamashita YM. Centrosome-centric view of asymmetric stem cell division. Open Biol. 2021; 11(1): 200314. [PMID: 33435817 DOI: 10.1098/rsob.200314]

[13] Sunchu B, Cabernard C . Principles and mechanisms of asymmetric cell division. Development 2020; 147(13): dev167650. [PMID: 32601056 DOI: 10.1242/dev.167650]

[14] Loeffler D, Wehling A, Schneiter F, Zhang Y, Müller-Bötticher N, Hoppe PS, et al. Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells. Nature 2019; 573(7774): 426-9. [PMID: 31485073 DOI: 10.1038/s41586-019-1531-6]

[15] Venkei ZG, Yamashita YM. Emerging mechanisms of asymmetric stem cell division. J Cell Biol 2018; 217(11): 3785-95. [PMID: 30232100 DOI: 10.1083/jcb.201807037]

[16] Kochendoerfer AM, Modafferi F, Dunleavy EM. Centromere function in asymmetric cell division in Drosophila female and male germline stem cells. Open Biol 2021; 11(11): 210107. [PMID: 34727723 DOI: 10.1098/rsob.210107]

[17] Sonkin D, Thomas A, Teicher BA. Cancer treatments: past, present, and future. Cancer Genet 2024; 286-287: 18-24. [PMID: 38909530 DOI 10.1016/j.cancergen.2024.06.002]

[18] Li R, Xiao C, Liu H, Huang Y, Dilger JP, Lin J. Effects of local anesthetics on breast cancer cell viability and migration. BMC Cancer 2018; 18(1): 666. [PMID: 29914426 DOI: 10.1186/s12885-018-4576-2]

[19] Liu H, Dilger JP, Lin J. The role of transient receptor potential melastatin 7 (TRPM7) in cell viability: a potential target to suppress breast cancer cell cycle. Cancers 2020; 12(1): 131. [PMID: 31947967 DOI: 10.3390/cancers12010131]

[20] Liu H, Weng J. A comprehensive bioinformatic analysis of cyclin-dependent kinase 2 (CDK2) in glioma. Gene 2022; 822: 146325. [PMID: 35183683 DOI: 10.1016/j.gene.2022.146325]

[21] Liu H, Weng J. A pan-cancer bioinformatic analysis of RAD51 regarding the values for diagnosis, prognosis, and therapeutic prediction. Front Oncol 2022; 12: 858756. [PMID: 35359409 DOI: 10.3389/fonc.2022.858756]

[22] Liu H, Li Y. Potential roles of cornichon family AMPA receptor auxiliary protein 4 (CNIH4) in head and neck squamous cell carcinoma. Cancer Biomark 2022; 35(4): 439-50. [PMID: 36404537 DOI: 10.3233/CBM-220143]

[23] Li Y, Liu H. Clinical powers of aminoacyl tRNA synthetase complex interacting multifunctional protein 1 (AIMP1) for head-neck squamous cell carcinoma. Cancer Biomark 2022; 34(3): 359-74. [PMID: 35068446 DOI: 10.3233/CBM-210340]

[24] Buss JH, Begnini KR, Lenz G. The contribution of asymmetric cell division to phenotypic heterogeneity in cancer. J Cell Sci 2024; 137(5): jcs261400. [PMID: 38334041 DOI: 10.1242/jcs.261400]

[25] Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 2006; 441(7097): 1068-74. [PMID: 16810241 DOI: 10.1038/nature04956]

[26] Yan K, Wang M, Qiu Z, Xu M. A cell model about symmetric and asymmetric stem cell division. J Theor Biol 2023; 560: 111380. [PMID: 36509138 DOI: 10.1016/j.jtbi.2022.111380]

[27] Li Z, Zhang YY, Zhang H, Yang J, Chen Y, Lu H. Asymmetric cell division and tumor heterogeneity. Front Cell Dev Biol 2022; 10: 938685. [PMID: 35859890 DOI: 10.3389/fcell.2022.938685]

[28] Chartier NT, Hyenne V, Labbé JC. Mechanisms of asymmetric cell division: from model organisms to tumorigenesis. Med Sci (Paris) 2010; 26(3): 251-7. [PMID: 20346274 DOI: 10.1051/medsci/2010263251]

[29] Zhang S, Wu S, Yao R, Wei X, Ohlstein B, Guo Z. Eclosion muscles secrete ecdysteroids to initiate asymmetric intestinal stem cell division in Drosophila. Dev Cell 2024; 59(1): 125-40.e112. [PMID: 38096823 DOI: 10.1016/j.devcel.2023.11.016]

[30] Mukherjee S, Kong J, Brat DJ. Cancer stem cell division: when the rules of asymmetry are broken. Stem Cells Dev 2015; 24(4): 405-16. [PMID: 25382732 DOI: 10.1089/scd.2014.0442]

[31] Mukherjee S, Brat DJ. Molecular programs underlying asymmetric stem cell division and their disruption in malignancy. Results Probl Cell Differ 2017; 61: 401-21. [PMID: 28409315 DOI: 10.1007/978-3-319-53150-2_18]

[32] Ferron SR, Pozo N, Laguna A, Aranda S, Porlan E, Moreno M, et al. Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling. Cell Stem Cell 2010; 7(3): 367-79. [PMID: 20804972 DOI: 10.1016/j.stem.2010.06.021]

[33] Wang YX, Feige P, Brun CE, Hekmatnejad B, Dumont NA, Renaud JM, et al. EGFR-Aurka signaling rescues polarity and regeneration defects in dystrophin-deficient muscle stem cells by increasing asymmetric divisions. Cell Stem Cell 2019; 24(3): 419-32.e416. [PMID: 30713094 DOI: 10.1016/j.stem.2019.01.002]

[34] Chan JR, Jolicoeur C, Yamauchi J, Elliott J, Fawcett JP, Ng BK, et al. The polarity protein Par-3 directly interacts with p75NTR to regulate myelination. Science 2006; 314(5800): 832-6.

[35] Koguchi M, Nakahara Y, Ito H, Wakamiya T, Yoshioka F, Ogata A, et al. BMP4 induces asymmetric cell division in human glioma stem-like cells. Oncol Lett 2020; 19(2): 1247-54. [PMID: 31966054 DOI: 10.3892/ol.2019.11231]

[36] Chen G, Kong J, Tucker-Burden C, Anand M, Rong Y, Rahman F, et al. Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma. Cancer Res 2014; 74(16): 4536-48. [PMID: 24947043 DOI: 10.1158/0008-5472.CAN-13-3703]

[37] Mukherjee S, Tucker-Burden C, Zhang C, Moberg K, Read R, Hadjipanayis C, et al. Drosophila Brat and human ortholog TRIM3 maintain stem cell equilibrium and suppress brain tumorigenesis by attenuating notch nuclear transport. Cancer Res 2016; 76(8): 2443-52. [PMID: 26893479 DOI: 10.1158/0008-5472.CAN-15-2299]

[38] Chen HF, Wu KJ. LncRNAs and asymmetric cell division: the epigenetic mechanisms. Biomed J 2024; 48(2): 100774. [PMID: 39059582 DOI: 10.1016/j.bj.2024.100774]

[39] Ma S, Wu J, Liu Z, He R, Wang Y, Liu L, et al. Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication. J Pharm Anal 2023; 13(4): 388-402. [PMID: 37181289 DOI: 10.1016/j.jpha.2023.03.002]

[40] Goetz LH, Schork NJ. Personalized medicine: motivation, challenges, and progress. Fertil Steril 2018; 109(6): 952-63. [PMID: 29935653 DOI: 10.1016/j.fertnstert.2018.05.006]

[41] Liu H, Dong A, Rasteh AM, Wang P, Weng J. Identification of the novel exhausted T cell CD8+ markers in breast cancer. Sci Rep 2024; 14(1): 19142. [PMID: 39160211 DOI: 10.1038/s41598-024-70184-1]

[42] Ai X, Smith MC, Feltus FA. Generative adversarial networks applied to gene expression analysis: an interdisciplinary perspective. Comput Syst Oncol. 2023; 3(3): e1050. [DOI: 10.1002/cso2.1050]

[43] Berika M, Elgayyar ME, El-Hashash AH. Asymmetric cell division of stem cells in the lung and other systems. Front Cell Dev Biol 2014; 2: 33. [PMID: 25364740 DOI: 10.3389/fcell.2014.00033]