CAMSAP2

Last updated
CAMSAP2
Identifiers
Aliases CAMSAP2 , CAMSAP1L1, calmodulin regulated spectrin associated protein family member 2
External IDs OMIM: 613775 MGI: 1922434 HomoloGene: 18927 GeneCards: CAMSAP2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001297707
NM_001297708
NM_203459
NM_001389638

NM_001081360
NM_001347109
NM_001347110

RefSeq (protein)

NP_001284636
NP_001284637
NP_982284

NP_001334038
NP_001334039

Location (UCSC) Chr 1: 200.74 – 200.86 Mb Chr 1: 136.2 – 136.27 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) is a protein in humans that is encoded by the CAMSAP2 gene. [5] CAMSAP2 possesses a microtubule-binding domain near the C-terminal region where "microtubule interactions" occur. On the C-terminal regions, protein to protein interactions are accelerated by three coiled-coil domains, which function as molecular spacers. [6] CAMSAP2 acts as a microtubule minus-end anchor and binds microtubules through its CKK domain. CAMSAP2 is necessary for the proper organization and stabilization of interphase microtubules. The protein also plays a role in cell migration. [7] CAMSAP2 stabilizes and attaches microtubule minus ends to the Golgi through the AKAP9 complex and myomegalin. CLASP1 proteins are responsible for microtubule stability which are not required for the Golgi tethering. When no centromeres are present, AKAP9 and CAMSAP-2 dependent pathways of the microtubule minus ends become a dominant force and must exist in order to observe the maintenance of microtubule density. [8]

Contents

3D rendering of the CAMSAP2 protein. CAMSAP2 protein render.png
3D rendering of the CAMSAP2 protein.

Structure

Microtubules are cytoskeletal polymers with structurally and functionally different ends. There exists a plus-end and a minus-end on each microtubule. The CAMSAP family of proteins contributes to regulating the minus-ends of microtubules. [12] CAMSAP2 contains a CKK domain that binds to microtubules. The specific CKK domain is a defining factor of the CAMSAP protein family. It enables CAMSAP2 to recognize and bind to microtubule minus ends and allows CAMSAP2 to decorate and stabilize the microtubule lattice formed by minus-end polymerization. [13] In addition to a CKK domain, CAMSAP2 contains an N-terminal calponin homology domain involved with actin binding. [14]

Function

Non-centrosomal microtubule maintenance

CAMSAP2 proteins are observed to be primarily responsible for the maintenance of non-centrosomal microtubules. In epithelial cells, major microtubules are not anchored to the centrosome, which can be observed in other cell types. CAMSAP2 cooperates with CAMSAP3 to achieve the organization observed in the non-centrosomal microtubules. They possess the ability to suppress the organization of microtubules by the centrosome, and the specific family of proteins is important for the suitable arrangement of organelles in the cell body. The proteins gathered at the minus ends of the non-centrosomal microtubules can stabilize them. Without these proteins, the Golgi apparatus would exhibit irregular distributions of the microtubules. [15]

Pancreatic islet cells

In pancreatic β-cells, glucose stimulation leads to the remodeling of microtubules responsible for insulin secretion. CAMSAP2 binds to the minus ends of microtubules in normal clonal cells. The knockdown of CAMSAP2 in the β-cells reduces the total insulin content secreted through glucose-stimulated insulin secretion. CAMSAP2 localizes to the Golgi apparatus instead of the microtubule minus ends. The oddity is observed only in β-cells as opposed to α-cells. With the specific collection at the Golgi apparatus, CAMSAP2 promotes the protein trafficking of the Golgi, efficiently facilitating the process. Without CAMSAP2, there would not be adequate insulin production for secretion from the β-cells. [16]

Migration

CAMSAP2-dependent microtubule organization promotes directional cell migration. CAMSAP2 is required for the proper organization of non-centrosomal interphase molecules. Depletion of CAMSAP2 leads to a mostly centrosome-anchored, radial microtubule array. CAMSAP2 is responsible for cell polarization because the stretches of CAMSAP2-decorated microtubules enable proper microtubule organization to achieve spatial redistribution and functional specialization of components in the cell. In wound healing assays, CAMSAP2 depletion reduced the ability of cells to close a wound, indicating impaired directional migration. [17] CAMSAP2 populates the cytoplasm with microtubules, allowing the cell to regenerate its cytoskeleton and facilitate effective cell migration.

Microtubule nucleation

Nucleation and aster formation activity of CAMSAP2. Observe the microtubule projections from the black dots (CAMSAP2 complexes). CAMSAP2 aster formation.jpg
Nucleation and aster formation activity of CAMSAP2. Observe the microtubule projections from the black dots (CAMSAP2 complexes).

The initial polymerization of microtubules can be called "microtubule nucleation". The process occurs spontaneously via soluble αβ-tubulin dimers. Microtubule nucleation normally requires overcoming a large energy barrier inside of cells. Typically, a γ-tubulin ring complex is recruited to facilitate the nucleation process; however, CAMSAP2 can act as a strong nucleating agent for microtubule formation independent of the γ-tubulin. CAMSAP2 significantly reduces the nucleation energy barrier by stabilizing longitudinal interactions between the αβ-tubulin dimers, thereby increasing the critical concentration for nucleation. CAMSAP2 achieves the increase by clustering with the αβ-tubulin dimers to generate intermediates from which multiple microtubules can originate, promoting new astral microtubule growth. [19]

Regulation

Regulator of neuronal polarity and development

CAMSAP2 is responsible for controlling axon specification and dendrite development. In the brain, neurons normally are not associated with any central microtubule-organizing centers (MTOC). The phenomenon sees the existence of free minus and plus-ends throughout the cell. CAMSAP2 has an affinity for binding to free microtubule minus ends in the cell. The stabilization CAMSAP2 can achieve by binding to the free ends of the microtubules is important in regulating neuronal polarity. The highly polarized neurons are formed in the developing neocortex, and the centrosome loses its function as an MTOC. CAMSAP2 structures' stability-providing qualities ensure the fate of the axon and the development of neuronal polarity needed for neocortex development. Neurons lacking CAMSAP2 fail to begin axon formation and lack neuronal polarization. [20]

Regulator of blood–testis barrier (BTB)

CAMSAP2 is involved in targeting microtubule minus-ends in Sertoli cell function. Sertoli cells are intrinsically polarized, with minus ends pointing toward the tubule lumen and plus ends toward the basement membrane of the seminiferous epithelium. [21] The protein was found throughout the Sertoli cell cytosol colocalized with microtubules. The Sertoli cells are responsible for regulating the blood-testis barrier. CAMSAP2 appears along the seminiferous epithelium close to the basement membrane. It increases the function of the Sertoli cell tight junction. All of the microtubule-based tracks in Sertoli cells are crucial for the intracellular transport of organelles. CAMSAP2 is bound to the minus-ends of microtubules, slowing down the polymerization of free tubulins and effectively regulating their growth. By knocking down CAMSAP2 proteins in these regions, the growth of the tracks could support spermatogenesis and BTB dynamics. In a model of Sertoli cell injury, a knockdown of the CAMSAP2 promoted Sertoli cell tight junction barrier function, which suggests its role in tight junction remodeling. CAMSAP2 knockdown blocked the disruptive organization of microtubules and actin filaments caused by the injury, enabling proper distribution of BTB-associated proteins at the cell junctions. [21]

Clinical research

Hepatocellular carcinoma (HCC)

CAMSAP2 plays a role in the migration of cancer cells. It has been observed that CAMSAP2 is severely upregulated in cancers such as hepatocellular carcinoma (HCC). When placed in an assay of liver samples, an outgrowth of HCC cells was observed. Upon the depletion of CAMSAP2 from the samples, a drop in the prevalence of acetylated microtubules occurred. CAMSAP2 exhibited tumor-suppressing qualities by downregulating the histone deacetylase 6 (HDAC6) promoter region. CAMSAP2 activates a c-Jun transrepression of HDAC6 along the Trio-dependent Rac1/JNK pathway, inhibiting CAMSAP2-mediated HCC metastasis. [22]

Colorectal cancer

CAMSAP2 promotes the migration of colorectal cancer cells by activating the JNK/c-Jun/MMP-1 signaling pathway. Acting as an oncogene, CAMSAP2 promotes the capabilities of migration in colorectal cells. Through the silencing of the gene, the substantial downstream target, MMP-1, regulated the invasion of the cells and slowed down disease progress. Metastasis of colorectal cancer permeates through the activation of the signaling pathway and indicates CAMSAP2 as a promising target for treating metastatic colorectal cancer patients. [23]

Gastric cancer

An association between CAMSAP2 expression levels and the progression and prognosis of gastric cancer was investigated in 2023. [24] The investigation into the expression of the CAMSAP2 protein in gastric cancer aimed to understand its effects on cell invasion and metastasis. [25] One hundred six cancer patients underwent a radical gastrectomy, and they analyzed the expression levels of CAMSAP2 proteins. Gastric cancer MGC803 cells with CAMSAP2 overexpression and knockdown were studied for epithelial-mesenchymal transition, where epithelial cells acquire the invasive characteristics of mesenchymal cells. Researchers utilized a nude mouse model with orthotopic gastric cancer cell xenografts to verify the in vitro results. The scientists discovered that gastric cancer tissues demonstrated high levels of CAMSAP2. The results positively correlated with tumor markers carcinoembryonic antigen and CA19-9. Bioinformatics analysis suggested CAMSAP2 is involved in epithelial-mesenchymal transition and the upregulation of TGF-β signaling. In the mouse model, CAMSAP2 overexpressing xenografts illustrated enhanced metastasis, increased vimentin and N-cadherin, and decreased E-cadherin. The high expression of CAMSAP2 contributes to gastric cancer progression and poor prognosis by the upregulation of TGF-β signaling. [24]

See also

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell division. The MTOC is a major site of microtubule nucleation and can be visualized in cells by immunohistochemical detection of γ-tubulin. The morphological characteristics of MTOCs vary between the different phyla and kingdoms. In animals, the two most important types of MTOCs are 1) the basal bodies associated with cilia and flagella and 2) the centrosome associated with spindle formation.

<span class="mw-page-title-main">Tubulin</span> Superfamily of proteins that make up microtubules

Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton. Microtubules function in many essential cellular processes, including mitosis. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division.

<span class="mw-page-title-main">Protein filament</span> Long chain of protein monomers

In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, strength, and rigidity to the cell. When the filaments are packed up together, they are able to form three different cellular parts. The three major classes of protein filaments that make up the cytoskeleton include: actin filaments, microtubules and intermediate filaments.

In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.

<span class="mw-page-title-main">Class III β-tubulin</span> Microtubule element of the tubulin family

Class III β-tubulin, otherwise known as βIII-tubulin (β3-tubulin) or β-tubulin III, is a microtubule element of the tubulin family found almost exclusively in neurons, and in testis cells. In humans, it is encoded by the TUBB3 gene.

<span class="mw-page-title-main">Tubulin alpha-1A chain</span> Protein-coding gene in the species Homo sapiens

Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.

<span class="mw-page-title-main">Ninein</span> Ninein (s.m. Al Ninein) in dialetto Bolognese è il maiale.

Ninein is a protein that in humans is encoded by the NIN gene.

<span class="mw-page-title-main">PCNT</span> Protein-coding gene in the species Homo sapiens

Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.

<span class="mw-page-title-main">TUBGCP2</span> Protein-coding gene in the species Homo sapiens

Gamma-tubulin complex component 2 is a protein that in humans is encoded by the TUBGCP2 gene. It is part of the gamma-tubulin complex, which is required for microtubule nucleation at the centrosome.

<span class="mw-page-title-main">Myomegalin</span> Vertebrate protein involved in the formation of microtubules

Myomegalin, also known as phosphodiesterase 4D-interacting protein or cardiomyopathy-associated protein 2, is a protein that in humans is encoded by the PDE4DIP gene. It has roles in the formation of microtubules from the centrosome. Its name derives from the fact that it is highly expressed in units of tubular myofibrils known as sarcomeres and is a large protein, at 2,324 amino acids. It was first characterised in 2000.

<span class="mw-page-title-main">CEP164</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein of 164 kDa, also known as CEP164, is a protein that in humans is encoded by the CEP164 gene. Its function appears two be twofold: CEP164 is required for primary cilium formation. Furthermore, it is an important component in the response to DNA damage by UV light.

<span class="mw-page-title-main">CEP76</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein of 76 kDa, also known as CEP76, is a protein that in humans is encoded by the CEP76 gene.

<span class="mw-page-title-main">CEP152</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein of 152 kDa, also known as Cep152, is a protein that in humans is encoded by the CEP152 gene. It is the ortholog of the Drosophila melanogaster gene asterless (asl) and both are required for centriole duplication.

<span class="mw-page-title-main">HOOK2</span> Protein-coding gene in the species Homo sapiens

Protein Hook homolog 2 (HK2) is a protein that in humans is encoded by the HOOK2 gene.

<span class="mw-page-title-main">AKNA</span> Protein-coding gene in the species Homo sapiens

AKNA is a protein that in humans is encoded by the AKNA gene. The protein is an AT-hook transcription factor which contains an AT-hook binding motif. The protein is expressed as different isoforms. AKNA is known to upregulate expression of the receptor CD40 and its ligand CD40L/CD154.

<span class="mw-page-title-main">TUBGCP4</span> Protein-coding gene in the species Homo sapiens

Tubulin, gamma complex associated protein 4 is a protein in humans that is encoded by the TUBGCP4 gene. It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome.

<span class="mw-page-title-main">Neurotubule</span>

Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of the neurotubules is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and the length of them can be adjusted by polymerization and depolymerization of tubulin.

<span class="mw-page-title-main">CAMSAP3</span> Microtubule minus-end binding human protein

Calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) is a human protein encoded by the gene CAMSAP3. The protein is commonly referred to as Nezha.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000118200 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041570 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "CAMSAP2 calmodulin regulated spectrin associated protein family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2024-02-27. Retrieved 2024-03-11.
  6. Mao BP, Ge R, Cheng CY (January 2020). "Role of microtubule +TIPs and -TIPs in spermatogenesis - Insights from studies of toxicant models". Reproductive Toxicology. 91: 43–52. doi:10.1016/j.reprotox.2019.11.006. PMID   31756440. Archived from the original on 2024-04-15. Retrieved 2024-04-15.
  7. Baines AJ, Bignone PA, King MD, Maggs AM, Bennett PM, Pinder JC, et al. (September 2009). "The CKK domain (DUF1781) binds microtubules and defines the CAMSAP/ssp4 family of animal proteins". Molecular Biology and Evolution. 26 (9): 2005–2014. doi:10.1093/molbev/msp115. PMID   19508979. Archived from the original on 2022-06-15. Retrieved 2022-09-29.
  8. Wu J, de Heus C, Liu Q, Bouchet BP, Noordstra I, Jiang K, et al. (October 2016). "Molecular Pathway of Microtubule Organization at the Golgi Apparatus". Developmental Cell. 39 (1): 44–60. doi:10.1016/j.devcel.2016.08.009. PMID   27666745. Archived from the original on 2024-04-15. Retrieved 2024-04-15.
  9. "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Archived from the original on 2022-10-01. Retrieved 2024-04-12.
  10. Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, et al. (January 2022). "AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models". Nucleic Acids Research. 50 (D1): D439–D444. doi:10.1093/nar/gkab1061. PMC   8728224 . PMID   34791371. Archived from the original on 2024-04-15. Retrieved 2024-04-15.
  11. Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. (August 2021). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873): 583–589. Bibcode:2021Natur.596..583J. doi:10.1038/s41586-021-03819-2. PMC   8371605 . PMID   34265844.
  12. Atherton J, Luo Y, Xiang S, Yang C, Rai A, Jiang K, et al. (2019-11-20). "Structural determinants of microtubule minus end preference in CAMSAP CKK domains". Nature Communications. 10 (1): 5236. Bibcode:2019NatCo..10.5236A. doi:10.1038/s41467-019-13247-6. ISSN   2041-1723. PMC   6868217 . PMID   31748546.
  13. "UniProt". www.uniprot.org. Archived from the original on 2024-04-15. Retrieved 2024-04-14.
  14. Jiang K, Hua S, Mohan R, Grigoriev I, Yau KW, Liu Q, et al. (February 2014). "Microtubule minus-end stabilization by polymerization-driven CAMSAP deposition". Developmental Cell. 28 (3): 295–309. doi: 10.1016/j.devcel.2014.01.001 . PMID   24486153.
  15. Tanaka N, Meng W, Nagae S, Takeichi M (December 2012). "Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules". Proceedings of the National Academy of Sciences of the United States of America. 109 (49): 20029–20034. Bibcode:2012PNAS..10920029T. doi: 10.1073/pnas.1218017109 . PMC   3523837 . PMID   23169647.
  16. Ho KH, Jayathilake A, Yagan M, Nour A, Osipovich AB, Magnuson MA, et al. (February 2023). "CAMSAP2 localizes to the Golgi in islet β-cells and facilitates Golgi-ER trafficking". iScience. 26 (2): 105938. Bibcode:2023iSci...26j5938H. doi:10.1016/j.isci.2023.105938. PMC   9883185 . PMID   36718359. Archived from the original on 2024-04-15. Retrieved 2024-04-15.
  17. Jiang K, Hua S, Mohan R, Grigoriev I, Yau KW, Liu Q, et al. (February 2014). "Microtubule minus-end stabilization by polymerization-driven CAMSAP deposition". Developmental Cell. 28 (3): 295–309. doi: 10.1016/j.devcel.2014.01.001 . PMID   24486153.
  18. Imasaki T, Kikkawa S, Niwa S, Saijo-Hamano Y, Shigematsu H, Aoyama K, et al. (June 2022). Carter AP, Pfeffer SR (eds.). "CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre through phase separation". eLife. 11: e77365. doi: 10.7554/eLife.77365 . PMC   9239687 . PMID   35762204.
  19. Imasaki T, Kikkawa S, Niwa S, Saijo-Hamano Y, Shigematsu H, Aoyama K, et al. (June 2022). "CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre through phase separation". eLife. 11. doi: 10.7554/eLife.77365 . PMC   9239687 . PMID   35762204.
  20. Yau KW, van Beuningen SF, Cunha-Ferreira I, Cloin BM, van Battum EY, Will L, et al. (June 2014). "Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development". Neuron. 82 (5): 1058–1073. doi: 10.1016/j.neuron.2014.04.019 . PMID   24908486.
  21. 1 2 Mao BP, Li L, Ge R, Li C, Wong CK, Silvestrini B, et al. (June 2019). "CAMSAP2 Is a Microtubule Minus-End Targeting Protein That Regulates BTB Dynamics Through Cytoskeletal Organization". Endocrinology. 160 (6): 1448–1467. doi:10.1210/en.2018-01097. PMC   6530524 . PMID   30994903.
  22. Li D, Ding X, Xie M, Huang Z, Han P, Tian D, et al. (2020-02-19). "CAMSAP2-mediated noncentrosomal microtubule acetylation drives hepatocellular carcinoma metastasis". Theranostics. 10 (8): 3749–3766. doi:10.7150/thno.42596. PMC   7069094 . PMID   32206120. Archived from the original on 2024-03-11. Retrieved 2024-04-15.
  23. Wang X, Liu Y, Ding Y, Feng G (October 2022). "CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway". Scientific Reports. 12 (1): 16899. Bibcode:2022NatSR..1216899W. doi:10.1038/s41598-022-21345-7. PMC   9546856 . PMID   36207462.
  24. 1 2 Zuo L, Wang L, Yang Z, Li J, Wang W, Li J, et al. (September 2023). "[High expression of CAMSAP2 promotes invasion and metastasis of gastric cancer cells by upregulating TGF-β signaling]". Nan Fang Yi Ke da Xue Xue Bao = Journal of Southern Medical University (in Chinese). 43 (9): 1460–1468. doi:10.12122/j.issn.1673-4254.2023.09.02. PMC   10563100 . PMID   37814859.
  25. Veiseh O, Kievit FM, Ellenbogen RG, Zhang M (February 2011). "Cancer Cell Invasion: Treatment and Monitoring Opportunities in Nanomedicine". Advanced Drug Delivery Reviews. 63 (8): 582–596. doi:10.1016/j.addr.2011.01.010. PMC   3132387 . PMID   21295093.

Further reading