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KISS1 in metastatic cancer research and treatment: potential and paradoxes

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Abstract

The significance of KISS1 goes beyond its original discovery as a metastasis suppressor. Its function as a neuropeptide involved in diverse physiologic processes is more well studied. Enthusiasm regarding KISS1 has cumulated in clinical trials in multiple fields related to reproduction and metabolism. But its cancer therapeutic space is unsettled. This review focuses on collating data from cancer and non-cancer fields in order to understand shared and disparate signaling that might inform clinical development in the cancer therapeutic and biomarker space. Research has focused on amino acid residues 68-121 (kisspeptin 54), binding to the KISS1 receptor and cellular responses. Evidence and counterevidence regarding this canonical pathway require closer look at the covariates so that the incredible potential of KISS1 can be realized.

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Abbreviations

DAG:

Diacylglycerol

E2 :

Estrogen

ER:

Estrogen receptor

ERK:

Extracellular signal-regulated kinase

FSH:

Follicle-stimulating hormone

GPCR:

G protein-coupled receptor

IP3:

Inositol trisphosphate

LH:

Luteinizing hormone

MAPK:

Mitogen activate protein kinase

PI3K:

Phosphatidylinositol 3-kinase

PIP2:

Phosphatidylinositol (4,5)-bisphosphate

PLC:

Phospholipase C

SNP:

Single-nucleotide polymorphism

TNBC:

Triple-negative breast cancer

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Acknowledgements

Work done in the authors’ labs was funded primarily by the National Foundation for Cancer Research; Susan G. Komen for the Cure (SAC110037); METAvivor Research and Support, Inc.; and USPHS-National Institutes of Health (Grant No. CA87728; CA134981); National Cancer Institute P30-CA168524 (DRW) and National Institutes of Health GM103418 and the KUMC Biomedical Research Training Program (TL); and the Hall Family Professorship in Molecular Medicine. We apologize to any authors whose work was omitted due to article guidelines. We are also grateful for helpful comments and suggestions from Thomas Beadnell, Rosalyn Zimmermann, and Adam Scheid.

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Authors and Affiliations

  1. Department of Cancer Biology, Kansas University Medical Center, 3901 Rainbow Blvd. - MS1071, Kansas City, KS, 66160, USA

    Thuc Ly & Danny R. Welch

  2. Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India

    Sitaram Harihar

  3. University of Kansas Cancer Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Danny R. Welch

Authors
  1. Thuc Ly
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  2. Sitaram Harihar
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  3. Danny R. Welch
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Corresponding author

Correspondence to Danny R. Welch.

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This review summarizes only published results from clinical studies. To the best of the authors’ knowledge, all studies were performed in compliance with applicable human subject protection policies, guidelines, and laws.

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This review summarizes only published results utilizing animals for experimental studies. All work from the authors’ laboratories was approved by relevant Institutional Animal Care and Use Committees. To the best of the authors’ knowledge, all other studies were performed in compliance with applicable policies, guidelines, and laws regarding humane housing, handling, and treatment of research animals.

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Ly, T., Harihar, S. & Welch, D.R. KISS1 in metastatic cancer research and treatment: potential and paradoxes. Cancer Metastasis Rev 39, 739–754 (2020). https://doi.org/10.1007/s10555-020-09868-9

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