By Jessica Lu
Cancer can be defined as a group of diseases characterised by uncontrolled cell division and genomic instability, eventually leading to dispersion to different sites (metastasis). In general, multicellular organisms are at risk of failure in the mechanisms that prevent continuous cell proliferation, leading to tumours (Doonan & Sablowski, 2010). Plants are multicellular organisms, as are animals, therefore both plants and animals have the potential to develop tumours. Despite this, plants are generally considered to not develop cancer. This is due to fundamental differences between plant tumours and animal tumours. Plant tumours do not metastasize and are rarely lethal, though they may still disrupt normal plant function and development (Doonan & Sablowski, 2010). On the other hand, animal tumours often become malignant, undergoing metastasis and becoming lethal (Seyfried & Huysentruyt, 2013).
Whilst the concept of oncogenes and proto-oncogenes is key to animal tumour genetics, it is poorly applicable to plants (Dodueva et al., 2020). Proto-oncogenes are normal cell genes that encode proteins that regulate the cell cycle and cell differentiation. When proto-oncogenes are mutated or overexpressed, they can become oncogenes, defined as genes that cause cancer. Plants and animals share similar mechanisms of cell cycle control, however, mutations in the genes involved in cell cycle control in plants tends not to cause tumour formation (Dodueva et al., 2020). For example, B-cyclin is a member of a family of proteins that work in conjunction with cyclin-dependent kinases (CDKs) to control the progression through the cell cycle (Doonan & Hunt, 1996). B-cyclin is only expressed during the G2 to M phase boundary of the cell cycle. Inserting extra copies of the B-cyclin gene into the genome of Arabidopsis plants under the At-cdc2a promoter (active in all proliferating cells) artificially boosted its expression. This increased root growth, however, it did not cause the formation of tumours (Doonan & Fobert, 1997).
Instead of via mutations to proto-oncogenes, most plant tumours are induced by pathogens. These pathogens include bacteria, double-stranded RNA viruses, fungi, the protist Plasmodiophora brassica, nematodes, and a variety of herbivorous insects (Dodueva et al., 2020). Usually these pathogens induce cell proliferation by shifting the hormonal balance in the tissues of the host plant. For example, the genes for the hormones indole-3-acetic acid (IAA) and cytokinins (CK) are also found in a variety of bacteria and fungi. IAA and CK are auxins, hormones which play key roles in plant growth and plant cell proliferation. Other pathogens may interfere with hormone transport, for example, some pathogenic bacteria have effector proteins which interact with IAA influx and efflux transporters (Dodueva et al., 2020).
Some plant varieties also develop spontaneous tumours at high frequency (Doonan & Sablowski, 2010), though these are significantly rarer that pathogen-induced tumours in vascular plants. Spontaneous tumours are defined as tumours that develop without pathogen-infection (Dodueva et al., 2020). Similarly to pathogen-induced tumours, the underlying cause is hormone dysfunction. One of the most susceptible genera of plants to spontaneous tumours is Nicotiana (tobacco) (Doonan & Sablowski, 2010). Although tumour-prone genotypes have been found in a wide range of plants, in most cases the genetic control of spontaneous tumours is poorly understood (Dodueva et al., 2020).
A major reason why plant tumours do not metastasise is because plant cells have cell walls, unlike animal cells (Doonan & Sablowski, 2010). The cell wall is a type of extracellular matrix (ECM), and is much more rigid than the ECM of an animal cell. The interaction between a cell and the ECM plays a key role in several steps of cancer progression. Because plant cells are fixed in a cell wall matrix, they are not motile and so metastasis is not possible. The ECM also helps maintain organised development. This is shown by the fact that mutations in tumorous shoot development (TSD) genes result in disorganised growth and perturbation of the meristem. TSD1 is involved in cellulose synthesis, whilst TSD2 affects cell adhesion (Doonan & Sablowski, 2010).
Even though plant tumours are rarely fatal, they are still important to study. One reason for this is that they can cause significant problems in agriculture by decreasing crop yield (Doonan & Sablowski, 2010; Escobar & Dandekar, 2003). For example, crown gall tumours are caused by Agrobacterium tumefaciens and related species. These tumours may be found on the stem or stem-root junction of several species. Crown gall disease decreases the productivity of horticultural crops such as grape, apple and cherry, likely because vascular damage at the site of the damage decreases water and nutrient flow. In addition, the rapidly dividing cells in the tumour use up water and nutrients which now cannot be used productively (Escobar & Dandekar, 2003). On the positive side, A. tumefaciens also has important uses in plant molecular biology. A. tumefaciens causes disease by transformation of a tumour-inducing (Ti) plasmid. By replacing oncogenes on Ti with a gene of interest, A. tumefaciens is a powerful plant genetic transformation tool (Hwang, Yu & Lai, 2017).
Overall, it is clear that plants do not get cancer in the same way that animals do. In fact, a specific definition of cancer for plants has been proposed to be the irreversible loss of organogenic totipotency (Gaspar, 1998). However, the study of plant tumours is still important for agriculture and has led to new discoveries in transformation biology.
References:
Dodueva, I. E., Lebedeva, M. A., Kuznetsova, K. A., Gancheva, M. S., Paponova, S. S. & Lutova, L. L. (2020) Plant tumors: a hundred years of study. Planta. 251 (4), 82. Available from: https://doi.org/10.1007/s00425-020-03375-5.
Doonan, J. & Fobert, P. (1997) Conserved and novel regulators of the plant cell cycle. Current Opinion in Cell Biology. 9 (6), 824-830. Available from: doi: https://doi.org/10.1016/S0955-0674(97)80083-X.
Doonan, J. & Hunt, T. (1996) Why don’t plants get cancer? Nature. 380 (6574), 481-482. Available from: https://doi.org/10.1038/380481a0.
Doonan, J. & Sablowski, R. (2010) Walls around tumours — why plants do not develop cancer. Nature Reviews Cancer. 10 (11), 794-802. Available from: https://doi.org/10.1038/nrc2942.
Escobar, M. A. & Dandekar, A. M. (2003) Agrobacterium tumefaciens as an agent of disease. Trends in Plant Science. 8 (8), 380-386. Available from: Available from: doi: https://doi.org/10.1016/S1360-1385(03)00162-6.
Gaspar, T. (1998) Plants can get cancer. Plant Physiology and Biochemistry. 36 (3), 203-204. Available from: Available from: doi: https://doi.org/10.1016/S0981-9428(97)86876-3.
Hwang, H., Yu, M. & Lai, E. (2017) Agrobacterium-Mediated Plant Transformation: Biology and Applications. The Arabidopsis Book. 2017 (15), Available from: https://doi.org/10.1199/tab.0186.
Seyfried, T. N. & Huysentruyt, L. C. (2013) On the origin of cancer metastasis. Critical Reviews in Oncogenesis. 18 (1-2), 43-73. Available from: doi: 3f85dd3739e1ad69,72fe0af97b0393c7 [pii].
Imperial Bioscience Review 