TITLE: Review of recent findings about anoikis and tumour metastasis

Authors: Abbas Jedariforoughi.

ABSTRACT:Anoikis is a critical mechanism for preventing ectopic cell growth or attachment to an inappropriate extracellular matrix, and also functions as a physiological barrier to cancer metastasis. Resistance to anoikis promotes tumor cell survival during the processes of local dissemination, systemic circulation and distant colonization.(2)

KEYWORDS:Anoikis. Tumour. cancer.isocitrate dehydrogenase 1 (IDH1) .liver kinase B1 (LKB1). glutamate dehydrogenase 1 (GDH1).Low Adherence Flow Cytometry Analysis (LAFCA) Assay.Low Adherence and Re-Attachment (LARA) Assay.Anchorage Independent Growth in Soft Agar (AIG-SA) assay. premetastatic niche.

Published in Doctmedico journal. Year:2021 volume:1 issue :2 page 160-163.

DOI : 10.17613/82yc-k387

Reviewed by : M. Asadiseyedmahaleh

REFERENCES:(Citation)

Title :review of recent findings about anoikis and tumour metastasis

abstract : Anoikis is a critical mechanism for preventing ectopic cell growth or attachment to an inappropriate extracellular matrix, and also functions as a physiological barrier to cancer metastasis. Resistance to anoikis promotes tumor cell survival during the processes of local dissemination, systemic circulation and distant colonization.(2)

Author: Dr Abbas Jedariforoughi MD

abbasjedari@yahoo.com

key words: Anoikis. Tumour. cancer.isocitrate dehydrogenase 1 (IDH1) .liver kinase B1 (LKB1). glutamate dehydrogenase 1 (GDH1).Low Adherence Flow Cytometry Analysis (LAFCA) Assay.Low Adherence and Re-Attachment (LARA) Assay.Anchorage Independent Growth in Soft Agar (AIG-SA) assay. premetastatic niche.

introduction:  Tumor metastasis is a major contributor to deaths from nearly all types of cancers. Anoikis, which is a form of programmed cell death resulting from loss of cell and extracellular membrane interaction, is known as a physiological barrier to metastasis.(1)

Cancer cells must develop anoikis resistance in order to survive in the circulation before forming metastatic foci in distant organs.(1)

Anoikis resistance is one of the hallmarks of cancer, which is essential for circulating tumor cells to persistently survive in the bloodstream and to exhibit the colonization/proliferation in the premetastatic niche (the favorable microenvironment for undifferentiated tumor-initiating cells to potentially form the distant metastatic disease) (9).

Anoikis is a type of apoptosis induced by cell detachment from the extracellular matrix (ECM), which removes mislocalized cells. Acquisition of anoikis resistance is critical for cancer cells to survive during circulation and, thus, metastasize at a secondary site. Although the sensitization of cancer cells to anoikis is a potential strategy to prevent metastasis, the mechanism underlying anoikis resistance is not well defined.(7)

Anchorage-independent growth and resistance to anoikis (cell death induced by loss of extracellular matrix attachment as in circulating metastatic cells) are essential features of disseminated cancer cells and metastatic progression (8).

discussion: In over 90% of the cases, cancer-related mortality is due to the formation of distant metastasis. Compared with the bulk of cancer cells in the primary site, metastatic cells have stronger abilities to escape the primary tumor, invade distant organs and adapt to novel microenvironmental conditions. Moreover, metastatic cells are often more resistant to anti-cancer therapies, which makes them more difficult to treat.(3)

Tissue homeostasis depends on many factors among which adequate interactions between cells and the surrounding extracellular matrix (ECM). Anoikis or cell homelessness is a detachment-induced cell death caused by loss of such interactions [1-3]. Dislodged cells undergo anoikis through a process involving integrin disengagements and, subsequently, the activation of specific intrinsic or extrinsic death pathways [4-6]. The intrinsic pathway leads to mitochondrial protein release into the cytosol and the activation of caspases proteins [7,8]. The extrinsic pathway is triggered by death ligands binding to their receptors and the activation of downstream signaling [9-12]. Both pathways ultimately lead to endonuclease activation, DNA degradation and dislodged cell death. (5)

Studies reveal that cancer cells switch from oxidative to reductive metabolism in utilizing glutamine during matrix detachment and support redox homeostasis via isocitrate dehydrogenase 1 (IDH1) .(1)

It is well understand the link between glutaminolysis and tumor metastasis. Studies screened for a factor in the glutaminolysis pathway that contributes to the acquisition of anoikis resistance, the prerequisite for metastasis.(1)

Interestingly, the cells that responded to glutaminolysis inhibition in terms of anoikis induction were commonly lacking LKB1. These data suggest that although GDH1 expression is induced upon detachment in all cells regardless of LKB1, glutaminolysis may be critical in protecting cells from anoikis only in lung cancer cells that lack LKB1.(1)

About one-third of lung cancer patient tumors lack or harbor inactive tumor suppressor liver kinase B1 (LKB1), and LKB1 deficiency is associated with increased metastatic rates and decreased survival in patients.(1)

Studies found that cultured HCC cells were more resistant to anoikis, which paralleled midkine expression, and midkine treatment significantly inhibited anoikis in a dose-dependent manner.(2)

Remarkably, although cancer cells reprogram metabolism to divert metabolites into the anabolic pathways that support proliferation [6,7,8,37,38,39], it has been shown that migratory/invasive cancer cells specifically favor mitochondrial respiration and increased ATP production.(4)

The arising interest in anoikis has led in the last few years to the development of several anoikis resistance assays. The LARA, LAFCA and AIG assays do not measure the same cell anoikis related  parameters.(5)

Studies conclude that IL-17A promotes migratory and angiogenic activity in tumors, enhances anoikis resistance, and modulates the immune landscape of the tumor microenvironment such changes favor cancer metastasis.(6)

Conclusion The acquisition of anoikis resistance allows tumor cells to survive while they circulate in the bloodstream and is vital to metastatic progression, but the molecular mechanism by which tumor cells develop anoikis resistance remains unclear.(1)

targeting GDH1 would be a promising therapeutic opportunity to prevent the development of metastasis in LKB1-deficient lung cancer.(1)

Anoikis resistance has been observed in various types of cancers in which anchorage‑independent growth is a crucial step for cancer metastasis. Therefore, agents interfering with this specific cancer cell behavior may be integrated into novel antimetastatic strategies. Monascin (MS), a secondary metabolite found in Monascus species, is a known potent chemopreventive compound used for treating metabolic complications; however, the effect of MS on anoikis resistance has not been investigated (10)

references: 

1)

Jin, Lingtao, et al. "The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer." Molecular cell 69.1 (2018): 87-99.

2)

Sun, Bin, et al. "Midkine promotes hepatocellular carcinoma metastasis by elevating anoikis resistance of circulating tumor cells." Oncotarget 8.20 (2017): 32523.

3)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354725/

4)

https://www.mdpi.com/2072-6694/12/1/22

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https://ideas.repec.org/a/abf/journl/v29y2020i2p22255-22262.html

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https://link.springer.com/article/10.1007/s00262-021-02867-x

7)

https://www.mdpi.com/2072-6694/13/2/247

8)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632686/

9)

https://www.pnas.org/content/115/33/E7652.short

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https://www.spandidos-publications.com/10.3892/ol.2020.12029

11)

https://cgp.iiarjournals.org/content/15/6/473.short

12)

https://www.nature.com/articles/cddis201768

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cm.21367?casa_token=1G-G02i2N2EAAAAA:BzIJoUzlycjrKMzRVzPiMyB-obGmhg65FsqbM-Sy-d3r14vtZgYBO06Esfi4ADJIVbr1TT-XP_ISMg

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https://www.biorxiv.org/content/10.1101/320739v2.abstract

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617412/

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https://cancerci.biomedcentral.com/articles/10.1186/s12935-021-01786-2

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https://cancerres.aacrjournals.org/content/78/13_Supplement/3447.short

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856897/

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https://academic.oup.com/jb/article-abstract/162/2/81/3828664

20)

https://www.researchsquare.com/article/rs-56413/latest.pdf

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https://cancerres.aacrjournals.org/content/79/13_Supplement/3486.short

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https://cancerres.aacrjournals.org/content/77/13_Supplement/5800.short

23)

https://ideas.repec.org/a/abf/journl/v29y2020i2p22255-22262.html