دورية أكاديمية
أعرض في EDS

Tumor suppressor PLK2 may serve as a biomarker in triple-negative breast cancer for improved response to PLK1 therapeutics.

التفاصيل البيبلوغرافية
العنوان: Tumor suppressor PLK2 may serve as a biomarker in triple-negative breast cancer for improved response to PLK1 therapeutics.
المؤلفون: Gao Y; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Kabotyanski EB; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Shepherd JH; The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Villegas E; University of Houston-Downtown, Houston, TX 77002, USA., Acosta D; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Hamor C; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Sun T; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Montmeyor-Garcia C; Canadian Blood Services, Toronto, ON M5G 2M1, Canada., He X; The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Dobrolecki LE; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Westbrook TF; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Lewis MT; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Hilsenbeck SG; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Zhang XH; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; McNair Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Perou CM; The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Rosen JM; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
المصدر: Cancer research communications [Cancer Res Commun] 2021 Dec; Vol. 1 (3), pp. 178-193. Date of Electronic Publication: 2021 Dec 27.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun
أسماء مطبوعة: Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]-
مواضيع طبية MeSH: Triple Negative Breast Neoplasms*/drug therapy, Humans ; Mice ; Animals ; Genes, Tumor Suppressor ; Biomarkers ; Protein Serine-Threonine Kinases/genetics
مستخلص: Polo-like kinase (PLK) family members play important roles in cell cycle regulation. The founding member PLK1 is oncogenic and preclinically validated as a cancer therapeutic target. Paradoxically, frequent loss of chromosome 5q11-35 which includes PLK2 is observed in basal-like breast cancer. In this study, we found that PLK2 was tumor suppressive in breast cancer, preferentially in basal-like and triple-negative breast cancer (TNBC) subtypes. Knockdown of PLK1 rescued phenotypes induced by PLK2-loss both in vitro and in vivo . We also demonstrated that PLK2 directly interacted with PLK1 at prometaphase through the kinase but not the polo-box domains of PLK2, suggesting PLK2 functioned at least partially through the interaction with PLK1. Furthermore, an improved treatment response was seen in both Plk2-deleted/low mouse preclinical and PDX TNBC models using the PLK1 inhibitor volasertib alone or in combination with carboplatin. Re-expression of PLK2 in an inducible PLK2-null mouse model reduced the therapeutic efficacy of volasertib. In summary, this study delineates the effects of chromosome 5q loss in TNBC that includes PLK2, the relationship between PLK2 and PLK1, and how this may render PLK2-deleted/low tumors more sensitive to PLK1 inhibition in combination with chemotherapy.
Competing Interests: Conflict of Interest: CMP is an equity stockholder and board member of BioClassifier and GeneCentric Therapeutics. CMP is also listed as an inventor on patent applications for the Breast PAM50. MTL is a Founder and Limited Partner of StemMed Ltd, and a Manager of StemMed Holdings, LLC, its General Partner. MTL is also a Founder of, and equity holder in, Tvardi Therapeutics Inc. The other authors declare that they have no competing interests.
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معلومات مُعتمدة: R01 CA148761 United States CA NCI NIH HHS; P50 CA058223 United States CA NCI NIH HHS; P30 CA125123 United States CA NCI NIH HHS; P30 DK056338 United States DK NIDDK NIH HHS; S10 RR024574 United States RR NCRR NIH HHS; T32 CA203690 United States CA NCI NIH HHS; P50 CA186784 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Biomarkers)
EC 2.7.11.- (PLK2 protein, human)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20220214 Date Completed: 20230727 Latest Revision: 20230727
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8827906
DOI: 10.1158/2767-9764.crc-21-0106
PMID: 35156101
قاعدة البيانات: MEDLINE
الوصف
تدمد:2767-9764
DOI:10.1158/2767-9764.crc-21-0106