Lamin A/C deficiency is an independent risk factor for cervical cancer

Capo-chichi, Callinice D.; Aguida, Blanche; Chabi, Nicodème W.; Cai, Qi; Offrin, Georges; Agossou, Vidéhouénou K.; Sanni, Ambaliou; Xu, Xiang Xi

doi:10.1007/s13402-015-0252-6

Cited by 19 publications

(41 citation statements)

References 44 publications

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“…Increasing reports indicate that altered lamin expression (rather than mutations) is found in many cancers, and often correlates with negative clinical outcomes [47,86,87]. For example, reduced expression of lamin A/C has been reported in breast [88,89] and cervical cancer [90], and is correlated with an increased recurrence of stage II and III colon cancer [91] and reduced disease free survival in breast cancer [89]. However, in other cases, increased A-type lamin expression is associated with disease progression, specifically in prostate, colon and ovarian cancers [92,93].…”

Section: Figurementioning

confidence: 99%

Squish and squeeze — the nucleus as a physical barrier during migration in confined environments

McGregor

Hsia

Lammerding

2016

Current Opinion in Cell Biology

200

152

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From embryonic development to cancer metastasis, cell migration plays a central role in health and disease. It is increasingly becoming apparent that cells migrating in three-dimensional (3-D) environments exhibit some striking differences compared with their well-established 2-D counterparts. One key finding is the significant role the nucleus plays during 3-D migration: when cells move in confined spaces, the cell body and nucleus must deform to squeeze through available spaces, and the deformability of the large and relatively rigid nucleus can become rate-limiting. In this review, we highlight recent findings regarding the role of nuclear mechanics in 3-D migration, including factors that govern nuclear deformability, and emerging mechanisms by which cells apply cytoskeletal forces to the nucleus to facilitate nuclear translocation. Intriguingly, the ‘physical barrier’ imposed by the nucleus also impacts cytoplasmic dynamics that affect cell migration and signaling, and changes in nuclear structure resulting from the mechanical forces acting on the nucleus during 3-D migration could further alter cellular function. These findings have broad relevance to the migration of both normal and cancerous cells inside living tissues, and motivate further research into the molecular details by which cells move their nuclei, as well as the consequences of the mechanical stress on the nucleus.

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Section: Figurementioning

confidence: 99%

Squish and squeeze — the nucleus as a physical barrier during migration in confined environments

McGregor

Hsia

Lammerding

2016

Current Opinion in Cell Biology

200

152

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“…18 Furthermore, this preliminary report indicates the loss of Lamin A/C can be detected in Papanicolaou sampling. 18 Thus, loss or greatly reduced nuclear envelope and lamina proteins likely account for significant nuclear deformation, the underlying principle for the Papanicolaou smear test. 1,2…”

Section: Introductionmentioning

confidence: 64%

“…Specifically, recent studies indicate that the loss of Lamin A/C proteins occurs in cervical cancer and may account for the nuclear shape changes . In a preliminary investigation of 50 archived human cervical carcinomas by immunohistochemistry, Lamin A/C was found lost in 70% of the cancer tissues, and abnormal distribution and patchy staining of Lamin A/C were seen in the other 30% .…”

Section: Deformed Nuclear Morphology and Loss Of Nuclear Structural Pmentioning

confidence: 98%

“…The collaboration between Lamin A and microtubules facilitates the nuclear shape, 17 Specifically, recent studies indicate that the loss of Lamin A/C proteins occurs in cervical cancer and may account for the nuclear shape changes. 18 In a preliminary investigation of 50 archived human cervical carcinomas by immunohistochemistry, Lamin A/C was found lost in 70% of the cancer tissues, and abnormal distribution and patchy staining of Lamin A/C were seen in the other 30%. 18 Furthermore, this preliminary report indicates the loss of Lamin A/C can be detected in Papanicolaou sampling.…”

Section: Introductionmentioning

confidence: 98%

“…18 In a preliminary investigation of 50 archived human cervical carcinomas by immunohistochemistry, Lamin A/C was found lost in 70% of the cancer tissues, and abnormal distribution and patchy staining of Lamin A/C were seen in the other 30%. 18 Furthermore, this preliminary report indicates the loss of Lamin A/C can be detected in Papanicolaou sampling. 18 Thus, loss or greatly reduced nuclear envelope and lamina proteins likely account for significant nuclear deformation, the underlying principle for the Papanicolaou smear test.…”

Section: Introductionmentioning

confidence: 98%

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New biological research and understanding of Papanicolaou's test

Smith

George

Kobetz

et al. 2018

Diagnostic Cytopathology

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The development of the Papanicolaou smear test by Dr. George Nicholas Papanicolaou (1883-1962) is one of the most significant achievements in screening for disease and cancer prevention in history. The Papanicolaou smear has been used for screening of cervical cancer since the 1950s. The test is technically straightforward and practical and based on a simple scientific observation: malignant cells have an aberrant nuclear morphology that can be distinguished from benign cells. Here, we review the scientific understanding that has been achieved and continues to be made on the causes and consequences of abnormal nuclear morphology, the basis of Dr. Papanicolaou's invention. The deformed nuclear shape is caused by the loss of lamina and nuclear envelope structural proteins. The consequences of a nuclear envelope defect include chromosomal numerical instability, altered chromatin organization and gene expression, and increased cell mobility because of a malleable nuclear envelope. HPV (Human Papilloma Virus) infection is recognized as the key etiology in the development of cervical cancer. Persistent HPV infection causes disruption of the nuclear lamina, which presents as a change in nuclear morphology detectable by a Papanicolaou smear. Thus, the causes and consequences of nuclear deformation are now linked to the mechanisms of viral carcinogenesis, and are still undergoing active investigation to reveal the details. Recently a statue was installed in front of the Papanicolaou's Cancer Research Building to honor the inventor. Remarkably, the invention nearly 60 years ago by Dr. Papanicolaou still exerts clinical impacts and inspires scientific inquiries.

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TPX2 promotes ovarian tumorigenesis by interacting with Lamin A/C and affecting its stability

et al. 2023

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Objective Ovarian cancer (OC) is one of the fatal gynecologic malignancies. However, there are no effective prognostic or therapeutic indicators for OC. Herein, we aim to reveal the potential function of targeting protein for Xklp2 (TPX2) in OC progression. Methods Immunohistochemical and bioinformatic analyses were used to evaluate the level of TPX2 in OC samples. Effects of TPX2 on cell proliferation, cell apoptosis and ROS production were evaluated in vivo and in vitro. Mass spectrometry, Co‐IP and immunofluorescence assays were performed to identify and verify protein‐protein interactions. Results Our data showed that pathological overexpression (OE) of the TPX2 in OC could manifest a poor prognosis. Functional studies demonstrated that TPX2 silencing led to the suppression of cell proliferation in vitro and in vivo through an increase in reactive oxygen species (ROS) level and apoptosis, while TPX2 OE exhibited the opposite effect. Furthermore, by mass spectrometric analysis, we identified a novel interacting partner, Lamin A/C, for TPX2. Mechanistically, TPX2 regulated Lamin A/C's stability by modulating the level of phospho‐Lamin A/C (Ser 22). Conclusion Our findings thus suggest that TPX2 may be a promising therapeutic target for OC.

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Lamin A/C deficiency is an independent risk factor for cervical cancer

Abstract: Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer.

Cited by 19 publications

References 44 publications

Squish and squeeze — the nucleus as a physical barrier during migration in confined environments

Squish and squeeze — the nucleus as a physical barrier during migration in confined environments

New biological research and understanding of Papanicolaou's test

TPX2 promotes ovarian tumorigenesis by interacting with Lamin A/C and affecting its stability

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