Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun;29(2):131-144.
doi: 10.1007/s10577-020-09646-x. Epub 2021 Jan 6.

Mitotic checkpoint defects: en route to cancer and drug resistance

Sinjini Sarkar  1   2 , Pranab Kumar Sahoo  1 , Sutapa Mahata  1 , Ranita Pal  1 , Dipanwita Ghosh  1 , Tanuma Mistry  1 , Sushmita Ghosh  1 , Tanmoy Bera  2 , Vilas D Nasare  3
Affiliations
Review

Mitotic checkpoint defects: en route to cancer and drug resistance

Sinjini Sarkar et al. Chromosome Res. 2021 Jun.

Abstract

Loss of mitosis regulation is a common feature of malignant cells that leads to aberrant cell division with inaccurate chromosome segregation. The mitotic checkpoint is responsible for faithful transmission of genetic material to the progeny. Defects in this checkpoint, such as mutations and changes in gene expression, lead to abnormal chromosome content or aneuploidy that may facilitate cancer development. Furthermore, a defective checkpoint response is indicated in the development of drug resistance to microtubule poisons that are used in treatment of various blood and solid cancers for several decades. Mitotic slippage and senescence are important cell fates that occur even with an active mitotic checkpoint and are held responsible for the resistance. However, contradictory findings in both the scenarios of carcinogenesis and drug resistance have aroused questions on whether mitotic checkpoint defects are truly responsible for these dismal outcomes. Here, we discuss the possible contribution of the faulty checkpoint signaling in cancer development and drug resistance, followed by the latest research on this pathway for better outcomes in cancer treatment.

Keywords: Carcinogenesis; Drug resistance; Microtubule targeting agents; Mitotic checkpoint; Spindle assembly checkpoint.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Allan LA, Camacho Reis M, Ciossani G et al (2020) Cyclin B1 scaffolds MAD1 at the kinetochore corona to activate the mitotic checkpoint. EMBO J 39(12):e103180. https://doi.org/10.15252/embj.2019103180 - DOI - PubMed - PMC
    1. Anderhub SJ, Mak GW, Gurden MD et al (2019) High proliferation rate and a compromised spindle assembly checkpoint confers sensitivity to the MPS1 inhibitor BOS172722 in triple-negative breast cancers. Mol Cancer Ther 18(10):1696–1707 - PubMed
    1. Balachandran RS, Heighington CS, Starostina NG, Anderson JW, Owen DL, Vasudevan S, Kipreos ET (2016) The ubiquitin ligase CRL2ZYG11 targets cyclin B1 for degradation in a conserved pathway that facilitates mitotic slippage. J Cell Biol 215(2):151–166 - PubMed - PMC
    1. Banerjee T, Nath S, Roychoudhury S (2009) DNA damage induced p53 downregulates Cdc20 by direct binding to its promoter causing chromatin remodeling. Nucleic Acids Res 37:2688–2698 - PubMed - PMC
    1. Bargiela-Iparraguirre J, Fernandez-Fuente, Herrera L., Calés C, Sanchez-Perez I. (2016) MAD2 in the spotlight as a cancer therapy regulator 3(2):1–6

Publication types

LinkOut - more resources