Abstract
It is commonly recognized in the field that cancer cells exhibit changes in the size and shape of their nuclei. These features often serve as important biomarkers in the diagnosis and prognosis of cancer patients. Nuclear size can significantly impact cell migration due to its incredibly large size. Nuclear structural changes are predicted to regulate cancer cell migration. Nuclear abnormalities are common across a vast spectrum of cancer types, regardless of tissue source, mutational spectrum, and signaling dependencies. The pervasiveness of nuclear alterations suggests that changes in nuclear structure may be crucially linked to the transformation process. The factors driving these nuclear abnormalities, and the functional consequences, are not completely understood. Nuclear envelope proteins play an important role in regulating nuclear size and structure in cancer. Altered expression of nuclear lamina proteins, including emerin, is found in many cancers and this expression is correlated with better clinical outcomes. A model is emerging whereby emerin, as well as other nuclear lamina proteins, binding to the nucleoskeleton regulates the nuclear structure to impact metastasis. In this model, emerin and lamins play a central role in metastatic transformation, since decreased emerin expression during transformation causes the nuclear structural defects required for increased cell migration, intravasation, and extravasation. Herein, we discuss the cellular functions of nuclear lamina proteins, with a particular focus on emerin, and how these functions impact cancer progression and metastasis.
Highlights
Some studies have indicated that nuclear envelope (NE) irregularities may be a direct result of oncogene activation, a lack of tumor suppressor function, or genomic instability [1,4,5]. These findings suggest that changes in the structure and composition of the NE may be regulated by events occurring early in the transformation process, and could be directly linked to tumorigenesis
Emerin binds a number of transcription regulators, including Germ Cell-Less (GCL) [59], Bcl-2 Associated Transcription Factor (Btf) [62], Lim Domain Only Protein 7 (Lmo7) [63], ß-catenin [64], SIKE [65], and barrier to autointegration factor (BAF) [52], and regulates the expression of their target genes
Components of developmental signaling pathways such as Wnt, Hedgehog, Hippo, and Notch can be affected, as can downstream nuclear targets of signaling pathways [113]. It is unclear if disruption of these key signaling pathways is caused by a loss of, or mutations in, emerin and to what extent this could contribute to cancer progression and metastasis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The INM contains a large number of integral INM proteins called NE transmembrane proteins that, together with the lamins, form the nuclear lamina [29,30], but what role these INM proteins play in regulating the nuclear structure remains to be elucidated. Tumor cells often show an aberrant nuclear structure, such as nuclear size and shape, number and sizes of nucleoli, and chromatin texture These alterations can be characteristic of a given tumor type and stage, and they are often used in cancer diagnosis [37]. These findings are relevant to invading cancer cells, which must move through tissues containing micron-sized spaces often smaller than the size of the nucleus. As changes in the NE correspond to functional changes in the nucleus, morphological changes in the nucleus are thought be involved in metastatic transformation
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