Cancer is a complex disease characterized by loss of control over cell growth, proliferation, and death. In addition to sustaining proliferative signaling and an unlimited replicative potential, many cancers cells acquire the ability to evade growth suppressors, resist cell death, induce angiogenesis, and activate invasion and metastasis (Hanahan and Weinberg, 2011). Moreover, cancer cells interact with surrounding stromal cell and remodel the extracellular matrix to construct specific tumor microenvironments that support tumor growth and progression (Egeblad et al., 2010; Kessenbrock et al., 2010; Lu et al., 2012). Of note, genomic instability raises the possibility to introduce genetic mutations, thus it is often crucial for tumorigenesis (Jeggo et al., 2016). The genetic mutations in cancer-related genes frequently lead to the dysregulation of oncogene activity or they inhibit the activity of a tumor suppressor gene, which then drive the oncogenic process forward. Although significant progress has been made in identifying driver mutations and associated oncogenic processes and pathways, the precise pathological mechanisms underlying tumorigenesis are still largely unclear. Increasing evidence now suggests links between oncogenic processes and the process of condensate assembly by phase separation.

In order to achieve spatiotemporal control over complex biochemical reactions, cells must organize proteins and other macromolecules into subcellular compartments. In addition to the classical membrane-bound organelles, such as the endoplasmic reticulum and Golgi apparatus, cells possess various membraneless compartments, including nucleoli, Cajal bodies, and promyelocytic leukemia protein (PML) bodies in the nucleus (Sawyer et al., 2019) as well as stress granules (SGs) or processing bodies (P bodies) in the cytoplasm (Banani et al., 2017; Jain et al., 2016; Sachdev et al., 2019; Wheeler et al., 2016). Recent studies suggest that the assembly of these membraneless compartments is often driven by a physical process known as phase separation (Banani et al., 2017; Boeynaems et al., 2018).

The term biomolecular condensates is now widely used to refer to membraneless intracellular compartments and assemblies (Banani et al., 2017; Shin and Brangwynne, 2017). In contrast to other types of assemblies, condensates have no fixed stoichiometry, they are able to concentrate molecules, and frequently form through phase separation. Phase separation is a process by which a well-mixed solution of macromolecules such as proteins or nucleic acids spontaneously separates into two phases: a dense and a dilute phase. The dense phase has liquid-like properties and enriches certain macromolecules while others are depleted, allowing the dense phase to function as a compartment (Alberti et al., 2019). After their formation by phase separation, liquid condensates can mature into more solid-like states. They can thus adopt a range of different material properties, from dynamic liquid-like droplets to non-dynamic gels and solid amyloids (Woodruff et al., 2018).

Proper condensate formation is essential for homeostasis as it provides cells with spatiotemporal control over protein function. Under some conditions, such as chronic stress, aging, or disease-associated mutations, abnormal or aberrant condensates can form. These condensates have compositions or properties that deviate from those of condensates formed under physiological conditions. Early research focused on cataracts, showing that phase separation of crystallin proteins in the eye lens causes opacification and thus visual impairment (Siezen and Benedek, 1985; Siezen et al., 1985; Tanaka et al., 1977). Excess accumulation of aberrant crystallin condensates during ageing was proposed to drive the formation of cataracts (Benedek, 1997). Recent studies showed that such aberrant phase transitions are also involved in neurodegenerative diseases, affecting neuronal proteins such as Fused in Sarcoma (FUS) in Amyotrophic Lateral Sclerosis (ALS) (Patel et al., 2015), Tau in Alzheimer's disease (AD) (Wegmann et al., 2018) and huntingtin exon 1 in Huntington's disease (HD) (Peskett et al., 2018). For example, patient mutations in FUS were shown to accelerate a transition of reconstituted FUS droplets from a liquid to a solid-like state (Patel et al., 2015). This hardening of FUS condensates is associated with the formation of supramolecular FUS fibrils that have properties of amyloid-like aggregates. Besides neurodegenerative disorders, current research further suggests emerging roles of aberrant condensates in cancer (Alberti and Dormann, 2019; Spannl et al., 2019).

This review summarizes our current understanding and recent findings regarding the formation, regulation, and function of biomolecular condensates and highlights their emerging roles in the pathogenesis of cancer.

Molecular features driving protein condensate formation

Recent work shows that phase separation requires the establishment of a network of interactions through multivalent protein molecules. These multivalent interactions are promoted by proteins containing multiple-folded modular domains or intrinsically disordered regions (IDRs) (Gomes and Shorter, 2019) or oligomerization domains (Dao et al., 2018; Figure 1). Another class of phase-separating proteins containing polymerizing domains such as the DIX domain, which assemble into filaments that are crosslinked into three-dimensional condensates (Bienz, 2020).

Figure 1

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Phase separation by proteins with folded modular domains was first established for two interacting proteins containing multiple copies of the SRC homology 3 (SH3) domains or the SH3 ligand proline-rich motifs (PRM) (Li et al., 2012). The study further demonstrated condensate formation by a three-component system containing the proteins nephrin, NCK, and neural Wiskott-Aldrich syndrome protein (N-WASP), and showed that phase separation by multiple SH3 containing protein NCK and multiple PRM containing protein N-WASP promoted Arp2/3-mediated actin assembly (Li et al., 2012). Multivalent interactions among multi-domain proteins were also shown to underlie the formation of membrane-associated phase-separated signaling clusters by T cell receptor (TCR) components (Ditlev et al., 2019; Huang et al., 2019; Su et al., 2016). The folded modular domains are often connected by intrinsically disordered linker sequences that determine the material properties of the formed condensates (Harmon et al., 2017).

Another class of proteins that has been implicated as drivers of condensate assembly is the class of proteins containing IDRs. Although IDRs lack a defined three-dimensional structure, they often harbor multiple short amino acid motifs that mediate weak interactions. These motifs have been called stickers because of their adhesive properties (Martin et al., 2020; Wang et al., 2018a). The driving forces for sticker-mediated interactions are π-π stacking, cation-π interactions, or charge-charge interactions (Nott et al., 2015; Vernon et al., 2018). The stickers within IDRs are connected by short sequences that are referred to as spacers. Spacers can affect the material properties of condensates. For instance, mutations in spacer residues in FUS changed the material properties of FUS condensates: glycine residues enhanced droplet fluidity, whereas glutamine and serine residues promoted hardening (Wang et al., 2018a).

IDRs that are enriched for only a few amino acids are referred to as low-complexity domains (LCDs) (Boeynaems et al., 2018). A subset of LCDs contains polar, uncharged amino acid residues, such as glutamine (Gln), asparagine (Asn), serine (Ser), or tyrosine (Tyr), and shows a compositional similarity to yeast prion domains (Alberti et al., 2009). These LCDs are referred to as prion-like domains (PLDs) and often found in RNA-binding proteins (RBPs). Proteins with PLDs have initially gained attention because of their ability to assemble into self-templating protein aggregates. These aggregates can have infectious properties, as they can spread between cells, tissues and sometimes individuals (Chakravarty and Jarosz, 2018). More recent studies suggest that PLDs can also act as drivers of condensate assembly. For example, the isolated PLDs of FUS (Burke et al., 2015; Murray et al., 2017), heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) (Kim et al., 2013) and flowering control locus A (FCA) (Fang et al., 2019) can assemble into condensates at high concentrations in vitro. However, whether PLDs drive phase separation by promoting homotypic PLD-PLD interactions in the cellular context is still unclear. In fact, evidence is emerging that PLDs often have to interact heterotypically with other IDRs during condensate assembly or they modulate the phase behavior of a protein by affecting its overall solubility. For example, phase separation of the FUS proteins was shown to require collective interactions among tyrosine residues in the PLD and arginine residues in the RNA-binding domain (RBD) (Wang et al., 2018a). Moreover, phase separation of the PLD-containing poly(A)-binding protein (Pab1 in yeast) is not mediated by its PLD, but by the RNA recognition motifs (RRMs). Rather, the PLD modulates condensate formation by the Pab1 RRM domains under heat shock condition (Riback et al., 2017). Thus, PLDs may not only be drivers but also modifiers of protein phase behavior (Franzmann and Alberti, 2019).

Finally, multivalent interactions can also arise from oligomerization of folded domains (Bienz, 2020; Dao et al., 2018; Fiedler et al., 2011; Madrzak et al., 2015; Schwarz-Romond et al., 2007). For example, UBQLN2, an adaptor protein required for cellular protein quality control, oligomerizes via the folded STI1-II domain and this promotes UBQLN2 phase separation (Dao et al., 2018).

One important question in the context of this review is whether proteins encoded by cancer-related genes (such as tumor-suppressors or oncogenes) can undergo the above-mentioned multivalent interactions and whether these interactions are perturbed in tumorigenesis. On the one hand, cancer-related mutations could disrupt the assembly of functional condensates by tumor-suppressors, thus contributing to the initiation of cancers. On the other hand, cancer-related mutations could promote the assembly of aberrant condensates by oncoproteins, which might stimulate tumorigenesis.

Speckle-type POZ protein (SPOP) condensates in degradation of oncogenic substrates

The tumor suppressor SPOP functions as a substrate adaptor of the cullin3 (CUL3)-RING ubiquitin ligase complex, which is frequently mutated in prostate cancer (Barbieri et al., 2012; Le Gallo et al., 2012). Tumor-associated missense mutations in the substrate recognition domain of SPOP disrupt substrate binding and ubiquitination, leading to the accumulation of oncogenic substrates, such as steroid receptor coactivator (SRC3), c-MYC (Geng et al., 2017) and death-domain-associated protein (DAXX) (Kwon et al., 2006). Bouchard et al. found that multivalent interactions between SPOP oligomers and motifs in oncogenic substrate proteins drive phase separation in vitro. The same multivalent interactions are required for SPOP co-localization with oncogenic substrates in nuclear condensates. Importantly, substrate proteins such as DAXX appear to be ubiquitylated inside the condensates in a CUL3-dependent manner. Consequently, cancer-associated SPOP mutations disrupt SPOP interaction with the substrates, causing a failure to form condensates, ubiquitylate the substrates and promote their degradation (Bouchard et al., 2018; Table 1 and Figure 2). These findings reveal a direct link between the aberrant phase behavior of a tumor suppressor protein and its downstream effects on oncogenic proteins.

Figure 2

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Condensates in the maintenance of genomic stability

Genomic instability usually arises from disruption of DNA repair and DNA damage response (DDR). Recent studies indicate that condensate assembly is linked to the maintenance of genomic stability. For instance, poly (ADP-ribose) polymerase 1 (PARP1) is one abundantly expressed member of the poly (ADP-ribose) polymerase (PARP) family. PARP1 synthesizes long PAR chains at DNA damage sites and plays a key role in DDR and PARP-1 has been ascribed diverse pro- or anti-tumorigenic roles (Weaver and Yang, 2013). The formation of PAR chains was shown to initiate the formation of DNA damage condensates via recruitment and assembly of FET proteins (FUS, EWS, and TAF15) (Altmeyer et al., 2015; Patel et al., 2015; Table 1; Figure 3).

Figure 3

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Additional studies have provided evidence for the involvement of condensates in maintaining genome stability. As one of the main mediators of the DNA damage response (DDR), p53-binding protein 1 (53BP1) acts as a recruitment platform for other DDR proteins (Mirza-Aghazadeh-Attari et al., 2019). 53BP1 protein was first discovered as a binding partner of the tumor suppressor p53 (Iwabuchi et al., 1994; Vousden and Prives, 2009) and plays a direct role in p53 target gene expression, driving a cell toward an anti- or pro-tumorigenic cell fate (Cuella-Martin et al., 2016). Loss of 53BP1 has been associated with poor survival, inhibition of apoptosis, and cancer cell proliferation in colorectal cancer (Bi et al., 2015).

Recently, 53BP1 was reported to drive the formation of a DNA damage repair compartment through phase separation in response to DNA damage, which was promoted by damage-induced long non-coding RNAs (dilncRNA) synthesized at DNA double-strand breaks (DSBs) (Kilic et al., 2019; Pessina et al., 2019; Table 1 and Figure 3). Blocking dilncRNA transcription or inhibiting DNA repair condensate assembly through the chemical 1,6-hexanediol both led to a reduction in the efficiency of DNA repair, suggesting that 53BP1 repair compartment assembly is required for DSB repair (Pessina et al., 2019). Importantly, these DNA damage repair condensates recruit downstream effectors, such as p53 and the p53 co-activator USP28, which stabilizes p53 upon DNA damage. As a consequence, disruption of DNA damage repair compartments led to impaired p53 induction and diminished p53 target gene expression as well as cell cycle arrest (Kilic et al., 2019; Figure 2). Therefore, aberrant DNA damage repair condensate assembly because of alterations in 53BP1 expression is likely to affect the central tumor suppressor protein p53 and thus the expression of many cancer-linked genes.

Intriguingly, 53BP1 is excluded from above-mentioned DNA damage condensates (Altmeyer et al., 2015). Given that 53BP1 is recruited to DNA damage sites later (Aleksandrov et al., 2018), this suggests that cells can assemble DNA damage condensates with different compositions and presumably also functions (Altmeyer et al., 2015). These studies suggest that condensate assembly is intimately linked to the maintenance of genome stability. Indeed, cancer-associated translocations in FET proteins appear to impair the cellular ability to interact with PAR chains, which may affect the assembly of condensates at DNA damage sites and thus undermine genome integrity (Altmeyer et al., 2015).

Transcriptional condensates in regulation of oncogenic transcriptional programs

Transcriptional dysregulation is a key feature of cancer (Figure 2). Recent studies have implicated condensates in the regulation of oncogenic transcription programs.

EWS-FLI1 is an oncogenic transcription factor that plays key roles in Ewing’s sarcoma tumorigenesis (Delattre et al., 1992). This oncogenic factor is generated by a chromosomal translocation, in which a large portion of the prion-like domain (PLD) of EWSR1 is fused to the transcription factor FLI1 in Ewing’s sarcoma (Tan and Manley, 2009; Toretsky and Wright, 2014). Rivera, Kadoch, and colleagues demonstrated that the translocated PLD was essential for recruiting the BRG1/BRM-associated factor (BAF) chromatin-remodeling complex to tumor-specific enhancers, activating an aberrant transcriptional cascades that is underlying Ewing sarcoma progression (Boulay et al., 2017; Table 1). Moreover, EWS-FLI1 forms numerous nuclear foci, whereas FLI1 exhibits a more diffuse pattern (Boulay et al., 2017). The hypothesis was put forward that this transcriptional program is driven by aberrant condensate formation of EWS-FLI1. In addition, the PLDs of the related proteins FUS and TAF15 are often fused to transcription factors through chromosomal translocations in liposarcoma and acute leukemia, respectively (Tan and Manley, 2009). It is possible that translocated FUS and TAF15 PLDs promote the assembly of additional aberrant condensates at enhancers and promoters, thus driving abnormal tumorigenic transcriptional programs.

Evidence is now also emerging that master transcription factors and the mediator coactivator use their disordered regions to form condensates at super-enhancers, which recruit Pol II to activate transcription sites (Boija et al., 2018; Cho et al., 2018; Sabari et al., 2018). In some cancer cells, genomic alterations promote the formation of super-enhancers at oncogenes, which promote oncogenic transcriptional programs (Sengupta and George, 2017). Thus, aberrant condensation at super-enhancers might be a general mechanism that cancer cells use to sustain high oncogene expression levels.

One example of a transcription regulator implicated in the assembly of a transcriptional condensates and super-enhancer formation is the transcriptional co-activator Yes-associated protein (YAP) and its paralog transcriptional coactivator with PDZ-binding motif (TAZ). YAP and TAZ have been linked to tissue growth, stem cell activity, and tumorigenesis (Moya and Halder, 2019). They bind to a subset of highly active enhancers and super-enhancers to drive the transcription of cell proliferation genes (Galli et al., 2015). Consequently, YAP and TAZ are pervasively activated in cancers (Zanconato et al., 2016; Zanconato et al., 2019). However, YAP and TAZ not only promote to tumorigenesis but also have tumor-suppressive functions. For example, activation of YAP in tumor-surrounding cells can suppress liver cancer in mice (Moya et al., 2019).

Recent evidence shows that YAP and TAZ assemble into condensates in vitro and in vivo (Cai et al., 2019; Lu et al., 2020; Table 1 and Figure 4). In cells, YAP assembles into condensates at super-enhancer regions and these nuclear condensates contain TAZ but also the transcription factor TEAD1. These condensates appear to recruit RNA polymerase II to trigger the transcription of proliferative genes (Cai et al., 2019). Furthermore, YAP and TAZ mutants defective in condensate formation, displayed reduced transcriptional activity, suggesting that transcriptional activity of YAP and TAZ is associated with their ability to assemble into condensates (Cai et al., 2019; Lu et al., 2020). Importantly, TAZ-containing condensates are negatively regulated by Hippo signaling and sensitive to mechanical signals (Lu et al., 2020). In agreement with this, a growing body of evidence suggests that YAP and TAZ could function as mechanotransducers, which detect a broad range of mechanical signals and convert them into cell-specific transcriptional responses (Panciera et al., 2017). In this way, YAP and TAZ could work as signaling hubs of the tumor microenvironment. For instance, YAP and TAZ expressed in cancer cells could sense physical cues from the surrounding microenvironment and respond by driving transcriptional programs that modify the composition and physical properties of the tumor microenvironment, thus promoting tumor development (Zanconato et al., 2019). Notably, in contrast to its diffuse localization in normal breast tissue, TAZ forms nuclear condensates in breast cancer tissue (Lu et al., 2020). Therefore, it would be interesting to investigate how the mechanical properties of tumor microenvironments affect YAP or TAZ phase separation and whether YAP/TAZ-driven tumorigenesis involves condensation in cancer cells.

Figure 4

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Condensates have not only been implicated in transcription activation, but also in transcription repression via epigenetic changes of chromatin. Indeed, epigenetic alterations in chromatin are well known to drive tumorigenesis (Flavahan et al., 2017). The first condensates that have been linked to gene silencing by heterochromatin formation are assembled from heterochromatin protein 1α (HP1α) (Larson et al., 2017; Strom et al., 2017). Another set of factors that is essential for the establishment and maintenance of facultative heterochromatin are the polycomb repressive complexes (PRC) (Tatavosian et al., 2019). These complexes also have oncogenic functions or they act as tumor suppressors, depending on the specific cancer type (Koppens and van Lohuizen, 2016). Chromobox 2 (CBX2), one subunit of Polycomb repressive complex 1 (PRC1), was recently shown to assemble into condensates that recruited the core subunits of the CBX2-PRC1 complex and directed the condensation of DNA and nucleosomes (Plys et al., 2019; Tatavosian et al., 2019; Table 1). These studies suggest that PRC1 condensates contribute to chromatin compaction, thus repressing the expression of PRC1 target genes. It will be intriguing to determine whether other epigenetic regulatory factors control the formation of gene regulatory condensates and whether impairment of epigenetic condensate control results in disease.

Signaling condensates in the regulation of signaling transduction

Signaling pathways play an essential role in regulating gene expression. Many membrane receptors and downstream signaling molecules assemble into two-dimensional (2D) clusters upon initiation of signaling (Bienz, 2014; Wu, 2013). Well-known examples are T cell receptor signaling clusters (Ditlev et al., 2019; Huang et al., 2019; Su et al., 2016) and clusters associated with adhesion receptors (Banjade and Rosen, 2014; Beutel et al., 2019; Case et al., 2019a; Li et al., 2012). The assembly of clusters on membranes is often important for the activation of downstream signaling effectors. For instance, phase separation of phosphorylated nephrin receptor together with its downstream effector molecules NCK and N-WASP promotes actin assembly. This enhancement of actin assembly was linked to the longer membrane dwell time of N-WASP in these clusters. More generally, the dwell time of cluster components was dependent on the composition of the cluster and the concentration of the cluster constituents (Case et al., 2019b), suggesting that there is an optimal condensate composition to reach full activation. Similarly, signaling condensates formed from the phosphorylated scaffold protein linker for activation of T cells (LAT) and its two adaptors growth factor receptor-bound protein 2 (GRB2) and Son of Sevenless homolog (SOS) promoted Ras activation by increasing membrane dwell time of SOS (Huang et al., 2019). Both cases suggest that increased dwell time of signaling effectors by condensation may be a general mechanism to fully activate a signaling pathway while at the same time ensuring signaling specificity.

Notably, GRB2, SOS, and some Ras isoforms are involved in downstream signaling effectors of epidermal growth factor receptor (EGFR). EGFR is frequently mutated or overexpressed in cancer cells (Sigismund et al., 2018) and abnormal activation of Ras in the EGFR pathway results in pro-tumorigenic proliferation and migration (Martinelli et al., 2017). Given that activation of EGFR is associated with membrane-bound clusters (Liang et al., 2018), it is very likely that EGFR condensate formation regulates pro-tumorigenic activation of Ras.

Components of other oncogenic signaling pathways appear to be able to form 2D clusters at the plasma membrane (Figure 2). One example is the Wnt/β-catenin signaling pathway, which governs numerous cell fate decisions during animal development, and is deregulated in many cancers in the colon, gastric, breast, and liver (Sanchez-Vega et al., 2018; Schaefer and Peifer, 2019; Zhan et al., 2017). In the absence of a Wnt signal, β-catenin is phosphorylated by a destruction complex, which is composed of Axin, tumor suppressor adenomatous polyposis coli (APC) and some additional components. Phosphorylated β-catenin is recognized by the Cullin-based E3 Ligase SCF^βTrCP, promoting the degradation of β-catenin by the proteasome (Stamos and Weis, 2013). In the presence of a Wnt signal, the activity of the destruction complex is repressed. Importantly, binding of Wnt to its cell surface receptors triggers the assembly of a signalosome, which is mediated by the Dishevelled (Dvl) protein (Bienz, 2020; Bilic et al., 2007; Fiedler et al., 2011; Gammons et al., 2016; Madrzak et al., 2015; Schwarz-Romond et al., 2007). The Axin complex is subsequently recruited to the signalosome, which destabilizes the destruction complex and blocks the phosphorylation of β-catenin (Stamos et al., 2014).

Increasing evidence suggests that both the destruction complex and Wnt signalosomes have properties of condensates (Schaefer and Peifer, 2019; Figure 5). In the absence of Wnt, Axin is found in cytoplasmic puncta which also contain APC as well as other destruction complex components (Schaefer et al., 2018). By contrast, in cells receiving Wnt signals, Dvl and Axin co-localize in puncta close to the plasma membrane (Cliffe et al., 2003). The assemblies grow by fusion (Kunttas-Tatli et al., 2014; Schwarz-Romond et al., 2005) and FRAP analysis further revealed that Dvl, Axin, and APC inside the puncta exchange dynamically (Pronobis et al., 2015; Schwarz-Romond et al., 2005). Importantly, the signaling activity of Dvl is strongly correlated with the ability to form these puncta (Schwarz-Romond et al., 2005). Similarly, puncta assembly is critical for destruction complex function (Faux et al., 2008; Schaefer and Peifer, 2019). APC is required for puncta assembly and cooperates with Axin to ensure efficient β-catenin destruction (Pronobis et al., 2015). Strikingly, mutations in APC, initiate >80% of colon cancers (Zhang and Shay, 2017). The precise mechanism of how these mutations promote tumorigenesis remains to be determined. There are numbers of additional urgent questions here, for example, how APC mutations affect the assembly and properties of destruction complex condensates and the relationship between aberrant destruction complex condensates and the initiation of cancers.

Figure 5

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Recent work has implicated condensates in another aspect of the Wnt signaling pathway. In the presence of Wnt, β-catenin accumulates in the nucleus and activates the transcription of Wnt target genes (Gammons and Bienz, 2018). Reports showed that β-catenin uses its IDRs to selectively partition into transcriptional condensates at super-enhancers (Zamudio et al., 2019; Table 1). Some cancer-related mutations in β-catenin prevent phosphorylation-dependent ubiquitination of β-catenin, leading to accumulation of β-catenin in the nucleus (Kim and Jeong, 2019). This suggests that in cancer cells, β-catenin may form aberrant nuclear condensates because of elevated protein levels and that this may promote tumorigenesis through widespread changes in gene expression.

Dysregulation of membraneless compartments in cancer

Accumulating evidence suggests that aberrant assembly of condensates is associated with cancer. How aberrant assembly and dysregulation of well-known membraneless compartments that form through condensation may promote tumorigenesis will be discussed in this section (Figure 6).

Figure 6

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Author details

1. Shan Jiang

   Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-1540-8506

2. Johan Bourghardt Fagman

   Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-1527-5280

3. Changyan Chen

   Department of Oncology at the Department of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-1546-4011

4. Simon Alberti

   Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany

   For correspondence

   alberti@mpi-cbg.de

   Competing interests

   is a scientific advisor of Dewpoint Therapeutics

   "This ORCID iD identifies the author of this article:" 0000-0003-4017-6505

5. Beidong Liu

   1. Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
   2. Center for Large-scale cell-based screening, Faculty of Science, University of Gothenburg, Gothenburg, Sweden

   For correspondence

   beidong.liu@cmb.gu.se

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-6052-8411

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