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Review
. 2019 Sep;38(3):493-506.
doi: 10.1007/s10555-019-09814-4.

KISS1 in breast cancer progression and autophagy

Ilya V Ulasov  1 , Anton V Borovjagin  2 , Peter Timashev  3 , Massimo Cristofanili  4 , Danny R Welch  5
Affiliations
Review

KISS1 in breast cancer progression and autophagy

Ilya V Ulasov et al. Cancer Metastasis Rev. 2019 Sep.

Abstract

Tumor suppressors are cellular proteins typically expressed in normal (non-cancer) cells that not only regulate such cellular functions as proliferation, migration and adhesion, but can also be secreted into extracellular space and serve as biomarkers for pathological conditions or tumor progression. KISS1, a precursor for several shorter peptides, known as metastin (Kisspeptin-54), Kisspeptin-14, Kisspeptin-13 and Kisspeptin-10, is one of those metastasis suppressor proteins, whose expression is commonly downregulated in the metastatic tumors of various origins. The commonly accepted role of KISS1 in metastatic tumor progression mechanism is the ability of this protein to suppress colonization of disseminated cancer cells in distant organs critical for the formation of the secondary tumor foci. Besides, recent evidence suggests involvement of KISS1 in the mechanisms of tumor angiogenesis, autophagy and apoptosis regulation, suggesting a possible role in both restricting and promoting cancer cell invasion. Here, we discuss the role of KISS1 in regulating metastases, the link between KISS1 expression and the autophagy-related biology of cancer cells and the perspectives of using KISS1 as a potential diagnostic marker for cancer progression as well as a new anti-cancer therapeutics.

Keywords: Autophagy; Brain tumor; Breast cancer metastases; KISS1 tumor suppressor.

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Conflict of interest statement

Conflict of interest Authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Comparative correlation of autophagy-related genes with KISS1 using GEO-deposed mRNA arrays.
The relative expression levels of KISS1, ATG5, ATG7, BECLIN1 and SQSTM1/P62 mRNAs in brain metastases of breast cancer and their correlation analyzed by using various mRNA platforms and data arrays deposed to GEO
Fig. 2
Fig. 2. A map of functional interactions (interactome) of KISS1 with various
brain metastatic cellular proteins. Previously reported interactions are shown by solid lines, whereas potential or predicted interactions are indicated by dashed lines. Subnetworks of upregulated (top) KISS1-interacting proteins (with expression profiles directly correlating with that of KISS1) are presented by 3 distinct cohorts grouped by color, each representing protein networks implicated in the following cellular functions: mechanisms of protein synthesis (red spheres), cellular metabolism involving mitochondrial proteins (green spheres), and cellular invasion mechanism (blue spheres). Downregulated proteins with expression profiles inversely correlating with that of KISS1 (bottom) do not fall into any distinct functional (color-grouped) cohorts and also exhibit a very few experimentally-evidenced/established functional links.
Fig. 3
Fig. 3. Ingenuity Pathway Analysis (IPA) for KISS1-regulated network.
KISS1-regulated network is associated with proteins, ions, RNA molecules and chemical compounds. KISS1 is positioned in the center of the protein network. The interacting proteins are depicted as various geometric shapes, each representing a particular functional class of proteins, whereas their position with regard to two horizontal solid lines reflects their compartmentalization properties/ intracellular localization, i.e. in the nucleus, cytoplasm or extracellular space. Proteins with unknown localization are positioned inside the vertical box on the right (“unknown”). The length and type of each protein-connecting line reflects either predicted (dashed line) or experimentally evidenced/published (solid line) interactions. Data were analyzed through the use of IPA (Ingenuity® Systems, http://www.ingenuity.com).
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