TY - JOUR
T1 - Defective nuclear lamina in aneuploidy and carcinogenesis
AU - Smith, Elizabeth R.
AU - Capochichi, Callinice D.
AU - Xu, Xiang Xi
N1 - Funding Information:
The studies from our lab cited in the review were partially supported by funds from the Jay Weiss Disparity Research and Developmental Research grant, and 2018 Inter-Program Pilot grant from UM/Sylvester Comprehensive Cancer Center. The work was also partially supported by a pilot grant from the University of Miami cFAR grant P30AI073961 from NIH. Grants 1R01CA230916-01, CA095071, CA099471, and CA79716 to X-XX from NCI-NIH and BC097189 and BC076832 from the DOD also contributed to the studies.
Publisher Copyright:
Copyright © 2018 Smith, Capo-chichi and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018
Y1 - 2018
N2 - Aneuploidy, loss or gain of whole chromosomes, is a prominent feature of carcinomas, and is generally considered to play an important role in the initiation and progression of cancer. In high-grade serous ovarian cancer, the only common gene aberration is the p53 point mutation, though extensive genomic perturbation is common due to severe aneuploidy, which presents as a deviant karyotype. Several mechanisms for the development of aneuploidy in cancer cells have been recognized, including chromosomal non-disjunction during mitosis, centrosome amplification, and more recently, nuclear envelope rupture at interphase. Many cancer types including ovarian cancer have lost or reduced expression of Lamin A/C, a structural component of the lamina matrix that underlies the nuclear envelope in differentiated cells. Several recent studies suggest that a nuclear lamina defect caused by the loss or reduction of Lamin A/C leads to failure in cytokinesis and formation of tetraploid cells, transient nuclear envelope rupture, and formation of nuclear protrusions and micronuclei during the cell cycle gap phase. Thus, loss and reduction of Lamin A/C underlies the two common features of cancer-aberrations in nuclear morphology and aneuploidy. We discuss here and emphasize the newly recognized mechanism of chromosomal instability due to the rupture of a defective nuclear lamina, which may account for the rapid genomic changes in carcinogenesis.
AB - Aneuploidy, loss or gain of whole chromosomes, is a prominent feature of carcinomas, and is generally considered to play an important role in the initiation and progression of cancer. In high-grade serous ovarian cancer, the only common gene aberration is the p53 point mutation, though extensive genomic perturbation is common due to severe aneuploidy, which presents as a deviant karyotype. Several mechanisms for the development of aneuploidy in cancer cells have been recognized, including chromosomal non-disjunction during mitosis, centrosome amplification, and more recently, nuclear envelope rupture at interphase. Many cancer types including ovarian cancer have lost or reduced expression of Lamin A/C, a structural component of the lamina matrix that underlies the nuclear envelope in differentiated cells. Several recent studies suggest that a nuclear lamina defect caused by the loss or reduction of Lamin A/C leads to failure in cytokinesis and formation of tetraploid cells, transient nuclear envelope rupture, and formation of nuclear protrusions and micronuclei during the cell cycle gap phase. Thus, loss and reduction of Lamin A/C underlies the two common features of cancer-aberrations in nuclear morphology and aneuploidy. We discuss here and emphasize the newly recognized mechanism of chromosomal instability due to the rupture of a defective nuclear lamina, which may account for the rapid genomic changes in carcinogenesis.
KW - Aneuploidy ovarian cancer
KW - Lamin A/C
KW - Nuclear budding
KW - Nuclear deformation
KW - Nuclear envelope
KW - Nuclear lamina
KW - Nuclear morphology
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U2 - 10.3389/fonc.2018.00529
DO - 10.3389/fonc.2018.00529
M3 - Review article
AN - SCOPUS:85063344430
VL - 8
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
IS - NOV
M1 - 529
ER -