Dormancy Mechanisms Research Articles

Effect of the photoperiod on bud dormancy in Liriodendron chinense

Bud dormancy and its release are complex physiological phenomena in plants. The molecular mechanisms of bud dormancy in Liriodendron chinense are mainly unknown. Here, we studied bud dormancy and the related physiological and molecular phenomena in Liriodendron under long-day (LD) and short-day (SD). Bud burst was released faster under LD than under SD. Abscisic acid (ABA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) activities were increased significantly under LD in Liriodendron buds. In contrast, the contents of gibberellic acid (GA3), ascorbic acid (AsA), glutathione (GSH), malondialdehyde (MDA), and ascorbate peroxidase (APX) activity decreased under LD but increased under SD. Differentially expressed genes (DEGs) were up-regulated under LD and down-regulated under SD and these changes correspondingly promoted (LD) or repressed (SD) cell division and the number and/or size of cells in the bud. Transcriptomic analysis of Liriodendron buds under different photoperiods identified 187 DEGs enriched in several pathways such as flavonoid biosynthesis and phenylpropanoid biosynthesis, plant hormone and signal transduction, etc. that are associated with antioxidant enzymes, non-enzymatic antioxidants, and subsequently promote the growth of the buds. Our findings provide novel insights into regulating bud dormancy via flavonoid and phenylpropanoid biosynthesis, plant hormone and signal transduction pathways, and ABA content. These physiological and biochemical traits would help detect bud dormancy in plants.

Isotopic evidence that aestivation allows malaria mosquitoes to persist through the dry season in the Sahel.

Data suggest that the malaria vector mosquito Anopheles coluzzii persists during the dry season in the Sahel through a dormancy mechanism known as aestivation; however, the contribution of aestivation compared with alternative strategies such as migration is unknown. Here we marked larval Anopheles mosquitoes in two Sahelian villages in Mali using deuterium (2H) to assess the contribution of aestivation to persistence of mosquitoes through the seven-month dry season. After an initial enrichment period, 33% of An. coluzzii mosquitoes were strongly marked. Seven months following enrichment, multiple analysis methods supported the ongoing presence of marked mosquitoes, compatible with the prediction that the fraction of marked mosquitoes should remain stable throughout the dry season if local aestivation is occurring. The results suggest that aestivation is a major persistence mechanism of An. coluzzii in the Sahel, contributing at least 20% of the adults at the onset of rains. This persistence strategy could influence mosquito control and malaria elimination campaigns.

Environmentally responsive reproduction: neuroendocrine signalling and the evolution of eusociality.

Eusociality is a rare but successful life-history strategy that is defined by the reproductive division of labour. In eusocial species, most females forgo their own reproduction to support that of a dominant female or queen. In many eusocial insects, worker reproduction is inhibited via dominance hierarchies or by pheromones produced by the queen and her brood. Here, we consider whether these cues may act as generic ‘environmental signals’, similar to temperature or nutrition stress, which induce a state of reproductive dormancy in some solitary insects. We review the recent findings regarding the mechanisms of reproductive dormancy in insects and highlight key gaps in our understanding of how environmental cues inhibit reproduction.

Effect of ageing on in vitro true seed and in vivo drupe germination and its dormancy mechanism in teak (Tectona grandis Linn.f)

The germination percentage of teak seed is generally very poor due to its higher percentage of empty seed and poor seed viability. The viable seeds exhibit protracted germination behaviour due to their inherent seed dormancy and other physiochemical characteristics. Hence establishing a teak nursery for largescale plantation activities is a challenging task. This study was undertaken to study the effect of ageing on in vitro true seed and in vivo drupe germination and its dormancy mechanism in teak. Fresh, one-year and two-year stored drupes were used to represent different levels of ageing. Under in vivo conditions, poor drupe germination was observed in fresh drupes (3%) and germination percentage was increased when the drupes were subjected to ageing for one year (17%) or two years (32%). When true seeds separated from fresh drupes and germinated under in vitro conditions, enhanced germination (58.3%) was observed. Biochemical analysis showed that indole-3- acetic acid, indole butyric acid, abscisic acid and coumarin are not present in fresh, one year and two-year-old true seeds. The gibberellic acid was increased with an increase in ageing, but the GA3 did not influence the germination percent under in vitro conditions. Scanning electron microscope (SEM) image of fresh teak true seed showed that embryo tip was shrivelled, whereas one and two-year-old true seed embryo tip bulged; this was confirmed that one and two-year-old true seed embryos were matured and satisfied the after-ripening requirement. Nursery studies revealed that one and two-year-old drupes recorded the highest germination compared to fresh drupes.

A dormancy mechanism limits metastasis of early spreading cancer cells.

A dormancy mechanism limits metastasis of early spreading cancer cells.

Temporal transcriptomics reveal the molecular mechanism of dormancy and germination regulated by temperature in Paris polyphylla seed

The mature seed of Paris polyphylla var. chinensis (PPC) is morphophysiologically dormant and develops differently under warm and cold temperatures. To elucidate the molecular mechanisms underlying temperature-dependent regulation of PPC seed dormancy and germination, we investigated the dynamic changes in PPC seed transcript levels under warm and cold temperature stratifications (WS and CS, respectively) by time-resolved RNA sequencing, focusing on genes related to hormone metabolism and signaling and cell wall remodeling (CWRM) and encoding transcription factors/regulators (TFs/TRs). A total of 48 765 and 47 836 differentially expressed genes (DEGs) were associated with WS and CS, respectively. Of these, 17 581 and 16 652 DEGs, respectively, unique to WS and CS, and 5 386 were common to both temperature stratifications across nine analyzed growth stages. The expression of hormone metabolism and signaling, TF/TR, and CWRM genes were closely associated with temperature. More genes related to gibberellin (GA), cytokinin, auxin, and brassinosteroid biosynthetic were upregulated in WS as compared to CS seeds, while genes related to dormancy release and germination were downregulated in WS seeds. However, only GA and abscisic acid levels were altered in PPC seeds breaking morphophysiological dormancy (MPD). Overall, 37 TF and five TR families were upregulated whereas 24 TF and 16 TR families were downregulated in WS as compared to CS seeds. Most CWRM families were highly expressed under WS as compared to CS, suggesting that they promote endosperm weakening and embryo growth of WS seeds and facilitate MPD release and germination. A coexpression analysis revealed positive correlations between TFs/TRs and DEGs involved in hormone metabolism and signaling and CWRM. These results provided a basis for investigating the interaction between the endosperm and underdeveloped embryo in the regulation of PPC seed germination and seedling emergence.

Comprehensive Biochemical, Physiological, and Transcriptomic Analyses Provide Insights Into Floral Bud Dormancy in Rhododendron delavayi Franch.

Due to a scarcity of relevant data, the ornamental woody flower Rhododendron delavayi Franch. is examined in the current study for its low temperature-induced floral bud dormancy (late October–end December) aspect. This study used transcriptome data profiling and co-expression network analyses to identify the interplay between endogenous hormones and bud dormancy phases such as pre-dormancy, para-dormancy, endo-dormancy, eco-dormancy, and dormancy release. The biochemical and physiological assays revealed the significance of the abundance of phytohormones (abscisic acid, auxin, zeatin, and gibberellins), carbohydrate metabolism, oxidative species, and proteins (soluble proteins, proline, and malondialdehyde) in the regulatory mechanism of floral bud dormancy. The transcriptome sequencing generated 65,531 transcripts, out of which 504, 514, 307, and 240 expressed transcripts were mapped uniquely to pre-, para-, endo-, and eco-phases of dormancy, showing their roles in the stimulation of dormancy. The transcripts related to LEA29, PGM, SAUR family, RPL9e, ATRX, FLOWERING LOCUS T, SERK1, ABFs, ASR2, and GID1 were identified as potential structural genes involved in floral bud dormancy. The transcription factors, including Zinc fingers, CAD, MADS-box family, MYB, and MYC2, revealed their potential regulatory roles concerning floral bud dormancy. The gene co-expression analysis highlighted essential hub genes involved in cold stress adaptations encoding proteins, viz, SERPIN, HMA, PMEI, LEA_2, TRX, PSBT, and AMAT. We exposed the connection among low temperature-induced dormancy in floral buds, differentially expressed genes, and hub genes via strict screening steps to escalate the confidence in selected genes as being truly putative in the pathways regulating bud dormancy mechanism. The identified candidate genes may prove worthy of further in-depth studies on molecular mechanisms involved in floral bud dormancy of Rhododendron species.

Exploiting Mouse Models to Recapitulate Clinical Tumor Dormancy and Recurrence in Breast Cancer.

Breast cancer recurrence and metastasis from activated dormant tumors remain the leading causes in disease morbidity. Women with estrogen receptor-positive breast cancer that accounts for nearly 80% of all cases face a lifelong risk of relapse after initial treatment. The biology of dormant tumors and dormant cancer cells that give rise to recurrent disease and metastasis remain to be understood for us to overcome the clinical challenges that they bring. The selection and optimization of preclinical models to recapitulate dormancy and recurrence in patients is critical for studying the underlying cellular and environmental factors. Here, we provide a brief review of studies that utilize mouse models to dissect the mechanisms of dormancy and therapeutic strategies to avert recurrence. This review specifically accentuates the versatility and benefits of immunocompetent transgenic mouse models that can be manipulated to recapitulate primary dormancy, metastatic dormancy, and post-therapy dormancy.

A quantitative analysis of temperature-dependent seasonal dormancy cycling in buried Arabidopsis thaliana seeds can predict seedling emergence in a global warming scenario.

Understanding how the environment regulates seed-bank dormancy changes is essential for forecasting seedling emergence in actual and future climatic scenarios, and to interpret studies of dormancy mechanisms at physiological and molecular levels. Here, we used a population threshold modelling approach to analyse dormancy changes through variations in the thermal range permissive for germination in buried seeds of Arabidopsis thaliana Cvi, a winter annual ecotype. Results showed that changes in dormancy level were mainly associated with variations in the higher limit of the thermal range permissive for germination. Changes in this limit were positively related to soil temperature during dormancy release and induction, and could be predicted using thermal time. From this, we developed a temperature-driven simulation to predict the fraction of the seed bank able to germinate in a realistic global warming scenario that approximated seedling emergence timing. Simulations predicted, in accordance with seedling emergence observed in the field, an increase in the fraction of the seed bank able to emerge as a result of global warming. In addition, our results suggest that buried seeds perceive changes in the variability of the mean daily soil temperature as the signal to change between dormancy release and induction according to the seasons.

Alkyne modified purines for assessment of activation of Plasmodium vivax hypnozoites and growth of pre-erythrocytic and erythrocytic stages in Plasmodium spp.

Malaria is a major global health problem which predominantly afflicts developing countries. Although many antimalarial therapies are currently available, the protozoan parasite causing this disease, Plasmodium spp., continues to evade eradication efforts. One biological phenomenon hampering eradication efforts is the parasite’s ability to arrest development, transform into a drug-insensitive form, and then resume growth post-therapy. Currently, the mechanisms by which the parasite enters arrested development, or dormancy, and later recrudesces or reactivates to continue development, are unknown and the malaria field lacks techniques to study these elusive mechanisms. Since Plasmodium spp. salvage purines for DNA synthesis, we hypothesised that alkyne-containing purine nucleosides could be used to develop a DNA synthesis marker which could be used to investigate mechanisms behind dormancy. Using copper-catalysed click chemistry methods, we observe incorporation of alkyne modified adenosine, inosine, and hypoxanthine in actively replicating asexual blood stages of Plasmodium falciparum and incorporation of modified adenosine in actively replicating liver stage schizonts of Plasmodium vivax. Notably, these modified purines were not incorporated in dormant liver stage hypnozoites, suggesting this marker could be used as a tool to differentiate replicating and non-replicating liver forms and, more broadly, as a tool for advancing our understanding of Plasmodium dormancy mechanisms.

Breaking Seed Dormancy of Jaltomata procumbens (Cav.) J. L. Gentry Seeds with the Use of KNO3

Jaltomata procumbens (Cav.) J. L. Gentry presents seed dormancy mechanisms in its two populations, erect and decumbent, that make its germination and obtaining of plants difficult. Potassium nitrate (KNO3) is used as a seed germination promoter by soaking in an osmotic solution. The objective was to break the dormancy of Jaltomata seeds by evaluating KNO3. Treatments included: 2 populations (erect and decumbent), 2 soaking times (4 and 6 days) in 2 concentrations of KNO3 solution (0.1% and 0.2%) and in distilled water used as a control. Days of germination including starting (DGS) and ending (DGE), energy period (EP), germination energy (GE), germination percentage (GP) and rate (GR) were measured. The erect population presented a more uniform germination and a lower number of DGS and DGE as well as 100% germination with the highest GR (2.56 seeds day−1). No statistical differences were observed between KNO3 and control; however, the positive effect of the KNO3 and 4 days of soaking on the germinated seed was observed. The decumbent population exhibited a more variable germination; however, the same trend of the solution type and soaking days was observed, reaching 93.1 GP. Considering the economic and accessibility aspects of substances that promote germination on J. procumbens, distilled water imbibition and KNO3 are recommended to accelerate the germination process.

Seed traits and phylogenomics: prospects for the 21st century

AbstractGenetic and biochemical studies have greatly advanced our understanding of the biology of seeds in recent years. Another area of study, which could accelerate contemporary seed biology research, is phylogenomics that integrates the wealth of genome sequence data with evolutionary biology. The recent phylogenomic study of the DELAY OF GERMINATION1 family genes exemplifies how the molecular evolution of seed genes can be traced back through early diverging plants and what implications can be obtained from the analysis of seed gene diversification at ancient times. The identification of possible ancestors of seed genes in non-seed plants could illuminate the ancient roots of the molecular mechanisms driving seed maturation programmes. It is possible that the origins of molecular mechanisms associated with the induction of seed storage proteins and desiccation tolerance proteins date back to the time of, or even prior to, early diverging land plants. Abscisic acid-dependent growth arrest or dormancy mechanisms might date back to red algae, one of the oldest algal groups. Thus, understanding algal cell biology will also be an integral part of future seed biology research. Unravelling key events associated with the evolution of seed- and non-seed plants will not only advance basic research but could also contribute to applied aspects of seed science, potentially leading to technology development for agriculture.

Effect of presowing seed treatments on teak (Tectona grandis L. F) drupes dormancy and germination

Poor seed germination is a major issue in teak (Tectona grandis) propagation. Teak seed dormancy is thought to be the reason for delayed germination. So far, specific dormancy mechanisms have not yet been identified. In order to study the influence of presowing treatments on germination, seedling vigour, and biochemical attributes of fresh teak drupes collected from the seed production area of Top Slip in Tamil Nadu. The collected drupes were subjected to different presowing treatments viz., T1 - control, T2 - soaking and drying for 6 days, T3 – T18 (soaking and drying for 5 days + soaking in different concentrations of thiourea, potassium nitrate, hydrogen peroxide and calcium oxychloride for 12 hours). Treated drupes were placed for germination in earthen pots and kept in open sunlight. In parallel, true seeds extracted from untreated drupes were also subjected to germination under in vitro conditions as a check. A higher percentage of germination (40%) was recorded in true seeds under in vitro conditions when compared to the treated and untreated drupes under in vivo conditions. Among the treated drupes sown under in vivo conditions, the drupes given soaking + drying for 5 days + soaking in 2% calcium oxychloride (CaOCl2) recorded higher germination (17.16) with better seedling vigour. Analysis of teak true seeds and mesocarp extract in high-performance liquid chromatography showed that gibberellic acid was found only in true seeds, whereas the other compounds, viz., indole-3-acetic acid, indole butyric acid, abscisic acid and coumarin, were not present in the true seed or mesocarp.

Considering therapy-induced senescence as a mechanism of tumour dormancy contributing to disease recurrence.

The capability of tumour cells to escape from therapy-induced senescence, as well as cell-non-autonomous functions of senescence, support the premise that senescence could serve as one pathway to tumour dormancy (among others that include quiescence and diapause) that is permissive for disease recurrence. Consequently, the pharmacologic targeting of senescent tumour cells could mitigate the risk for cancer resurgence, thereby enhancing the therapeutic efficacy of cancer chemotherapy.

Single-cell sequencing reveals MYC targeting gene MAD2L1 is associated with prostate cancer bone metastasis tumor dormancy

BackgroundAmong malignant tumors, bone metastasis is frequently associated with prostate cancer which is seen in about 80% of patients. During cancer treatments, some tumor cells switch to a "dormant mode" to help tumor cells avoid attack from the immune system and anti-tumor therapies. In this dormant mode, tumor cells can be resuscitated, causing cancer to reoccur. The generally accepted explanation for this phenomenon is that the tumor cells have spread to the bone marrow before treatment and are dormant in the bone marrow. However, the key mechanism for inducing and maintaining the dormancy of these prostate cancer disseminated tumor cells in the bone marrow is still unclear. Therefore, studying the dormancy mechanism of tumor cells in bone metastasis is of great significance for the treatment and the prevention of recurrence of prostate cancer.MethodsWe obtained single-cell RNA-seq data of tumors from mouse models of prostate cancer bone metastasis mouse model numbered (GSE147150) from the GEO database, and obtained RNA-seq expression data and clinical information from The Cancer Genome Atlas Program (TCGA) of prostate cancer patients from the USCS Xena database. Screening of differential genes and annotation of GO functions were performed separately. Subsequently, the screened differential genes were compared and analyzed with 50 classic Hallmark signaling pathways, and the prognosis analysis of prostate cancer patients in TCGA data was performed to discover the key genes of the dormant mechanism of tumor cells in bone metastasis, and obtain new biomarkers that can be used to predict the prognosis of patients.ResultsA total of 378 differentially expressed genes were screened, of which 293 were significantly up-regulated and 85 were significantly down-regulated. Among them, the up-regulated genes were mainly related to the immune response, and the down-regulated genes were mainly related to the cell cycle. Through GSVA (Gene set variation analysis), it is found that there are differences in a total of 3 signal pathways: COMPLEMENT, MYC_TARGETS_V1 and MYC_TARGETS_V2. By comparing and analyzing the significantly down-regulated genes in dormant tumor cells with MYC_TARGETS_V1, MYC_TARGETS_V2, three significantly down-regulated genes were obtained: Ccna2, Mad2L1 and Plk1.ConclusionIn summary, our findings indicate that the MYC targeting gene Mad2L1 is potentially related to the dormancy mechanism of prostate cancer. At the same time, Mad2L1, a gene associated with dormant prostate cancer cells, may be used as a biomarker for prognostic survival.

Hybrid RNA Sequencing Strategy for the Dynamic Transcriptomes of Winter Dormancy in an Evergreen Herbaceous Perennial, Iris japonica.

Japanese iris (Iris japonica) is a popular perennial ornamental that originated in China; it has a long display period and remains green outdoors throughout the year. winter dormancy characteristics contribute greatly to the evergreenness of herbaceous perennials. Thus, it is crucial to explore the mechanism of winter dormancy in this evergreen herbaceous perennial. Here, we used the hybrid RNA-seq strategy including single-molecule real-time (SMRT) and next-generation sequencing (NGS) technologies to generate large-scale Full-length transcripts to examine the shoot apical meristems of Japanese iris. A total of 10.57 Gb clean data for SMRT and over 142 Gb clean data for NGS were generated. Using hybrid error correction, 58,654 full-length transcripts were acquired and comprehensively analysed, and their expression levels were validated by real-time qPCR. This is the first full-length RNA-seq study in the Iris genus; our results provide a valuable resource and improve understanding of RNA processing in this genus, for which little genomic information is available as yet. In addition, our data will facilitate in-depth analyses of winter dormancy mechanisms in herbaceous perennials, especially evergreen monocotyledons.

Novel Dormancy Mechanism of Castration Resistance in Bone Metastatic Prostate Cancer Organoids.

Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

Photothermal controls of vegetative dormancy in Poa secunda

AbstractBackgroundSummer vegetative dormancy is a desirable trait in cool‐season grasses when they are interplanted with annual crops. Sandberg bluegrass (Poa secunda J. Presl.) shows summer dormancy, but the environmental cues that control dormancy remain unknown.MethodsA controlled environment study using temperature and day length combinations of 32.2°C/15 h, 26.6°C/14 h, 21.1°C/13 h, and 15.5°C/12 h was conducted with P. secunda accessions PI232347, PI639272, and PI232348, and ‘Audubon’ red fescue as a nondormant control to determine the optimum treatment for dormancy induction. A second study using treatments of 26.6°C/14 h, 21.1°C/13 h, and 15.5°C/12 h was conducted to determine the thresholds for dormancy release. A third study used a factorial experiment with two temperatures (32.2°C and 15.5°C) and two day lengths (15 and 12 h) to differentiate between temperature and day length effects on dormancy induction.ResultsOf the four temperature and day length combinations, all except for 15.5°C/12 h resulted in dormancy by the end of 6 weeks, with 32.2°C/15 h inducing dormancy in only 17 days. Of the three treatments for dormancy release, 15.5°C/12 h broke dormancy the fastest in all accessions and released the most number of plants from dormancy. Considerable variation existed between accessions for the speed of dormancy release in the 21.1°C/13 h and 26.6°C/14 h treatments. The third study showed that temperature is the primary inducer for summer dormancy, while longer day length may promote dormancy under inductive temperatures.ConclusionsThis study identified the optimum photothermal for induction and release of summer dormancy in P. secunda, which will help future studies in elucidating the mechanism of summer dormancy.

Recruitment of pioneer trees with physically dormant seeds under climate change: the case of Vachellia pennatula (Fabaceae) in semiarid environments of Mexico.

Most tree species native to arid and semiarid ecosystems produce seeds with physical dormancy, which have impermeable coats that protect them from desiccation and prevent germination when the environmental conditions are unfavorable for seedling establishment. This dormancy mechanism may confer some degree of tolerance to seeds facing warmer and drier conditions, as those expected in several regions of the world because of climate change. Scarification of these seeds (removal of protective coats) is required for stimulating germination and seedling development. However, as scarification exposes seeds to the external environmental conditions, it can promote desiccation and viability loss in the future. To test these hypotheses, we performed field experiments and sowed scarified and unscarified seeds of a pioneer tree native to semiarid ecosystems of Mesoamerica (Vachellia pennatula) under the current climate and simulated climate change conditions. The experiments were conducted at abandoned fields using open-top chambers to increase temperature and rainout shelters to reduce rainfall. We measured microenvironmental conditions within the experimental plots and monitored seedling emergence and survival during a year. Air temperature and rainfall in climate change simulations approached the values expected for the period 2041-2080. Seedling emergence rates under these climatic conditions were lower than under the current climate. Nevertheless, emergence rates in climate change simulations were even lower for scarified than for unscarified seeds, while the converse occurred under the current climate. On the other hand, although survival rates in climate change simulations were lower than under the current climate, no effects of the scarification treatment were found. In this way, our study suggests that climate change will impair the recruitment of pioneer trees in semiarid environments, even if they produce seeds with physical dormancy, but also indicates that these negative effects will be stronger if seeds are scarified.

Tumor Dormancy: Biologic and Therapeutic Implications.

Metastatic cancer can arise years after treatment of the primary tumor because residual tumor cells can enter dormancy and evade elimination by anti-neoplastic therapies. The mechanisms underlying this phenomenon have been investigated and a number of hypotheses have been proposed. Tumor mass dormancy involves a balance between apoptotic and proliferative cells, keeping a micrometastatic lesion constant in size. This induces a need for blood supply which involves angiogenic dormancy. Cellular dormancy is also considered a mechanism of dormancy, where dormancy is induced due to cells entering a quiescent, reversible, growth-arrested state. In addition to all of these mechanisms, important changes in the tumor microenvironment, including the extracellular matrix, the oxygenation levels of the environment, and endoplasmic reticulum stress, are involved in inducing and maintaining tumor dormancy. Since dormant tumors are commonly known to be resistant to chemotherapy, gaining more knowledge of the mechanism of dormant tumor cells is of importance, as it can lead to the development of future treatment strategies.