scholarly journals KIBRA (WWC1) Is a Metastasis Suppressor Gene Affected by Chromosome 5q Loss in Triple-Negative Breast Cancer

Cell Reports ◽  
2018 ◽  
Vol 22 (12) ◽  
pp. 3191-3205 ◽  
Author(s):  
Jennifer F. Knight ◽  
Vanessa Y.C. Sung ◽  
Elena Kuzmin ◽  
Amber L. Couzens ◽  
Danielle A. de Verteuil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Suppressor Gene ◽  
Metastasis Suppressor ◽  
Metastasis Suppressor Gene ◽  
Chromosome 5Q

scholarly journals ROLE OF TUMOUR SUPPRESSOR GENE P53 IN TRIPLE NEGATIVE BREAST CANCER

2017 ◽  
Vol 5 (4.2) ◽  
pp. 4585-4589
Author(s):  
Priya S Patil ◽  
◽  
Jaydeep N Pol ◽  
Ashalata D Patil ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor

scholarly journals Genetic Polymorphisms of Metastasis Suppressor Gene NME1 and Breast Cancer Survival

2008 ◽  
Vol 14 (15) ◽  
pp. 4787-4793 ◽  
Author(s):  
Shimian Qu ◽  
Jirong Long ◽  
Qiuyin Cai ◽  
Xiao-Ou Shu ◽  
Hui Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Polymorphisms ◽  
Cancer Survival ◽  
Suppressor Gene ◽  
Breast Cancer Survival ◽  
Metastasis Suppressor ◽  
Metastasis Suppressor Gene

EcoRI polymorphism of the metastasis-suppressor gene NME1 in Mexican patients with breast cancer

2005 ◽  
Vol 96 (2) ◽  
pp. 159-161 ◽  
Author(s):  
Susan Andrea Gutierrez Rubio ◽  
Silvia Esperanza Flores Martinez ◽  
Jose Sanchez Corona ◽  
Adriana Patricia Mendizabal Ruiz ◽  
Angel Emilio Suarez Rincon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Suppressor Gene ◽  
Metastasis Suppressor ◽  
Metastasis Suppressor Gene ◽  
Mexican Patients

scholarly journals TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer

2019 ◽  
Vol 41 (3) ◽  
pp. 313-325 ◽  
Author(s):  
David Peeney ◽  
Sandra M Jensen ◽  
Nadia P Castro ◽  
Sarvesh Kumar ◽  
Silvia Noonan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Metastasis Suppressor ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

Abstract Metastasis is the primary cause of treatment failures and mortality in most cancers. Triple-negative breast cancer (TNBC) is refractory to treatment and rapidly progresses to disseminated disease. We utilized an orthotopic mouse model that molecularly and phenotypically resembles human TNBC to study the effects of exogenous, daily tissue inhibitor of metalloproteinase-2 (TIMP-2) treatment on tumor growth and metastasis. Our results demonstrated that TIMP-2 treatment maximally suppressed primary tumor growth by ~36–50% and pulmonary metastasis by >92%. Immunostaining assays confirmed disruption of the epithelial to mesenchymal transition (EMT) and promotion of vascular integrity in primary tumor tissues. Immunostaining and RNA sequencing analysis of lung tissue lysates from tumor-bearing mice identified significant changes associated with metastatic colony formation. Specifically, TIMP-2 treatment disrupts periostin localization and critical cell-signaling pathways, including canonical Wnt signaling involved in EMT, as well as PI3K signaling, which modulates proliferative and metastatic behavior through p27 phosphorylation/localization. In conclusion, our study provides evidence in support of a role for TIMP-2 in suppression of triple-negative breast cancer growth and metastasis through modulation of the epithelial to mesenchymal transition, vascular normalization, and signaling pathways associated with metastatic outgrowth. Our findings suggest that TIMP-2, a constituent of the extracellular matrix in normal tissues, may have both direct and systemic antitumor and metastasis suppressor effects, suggesting potential utility in the clinical management of breast cancer progression.

scholarly journals Tumor Suppressor PLK2 May Serve as a Biomarker in Triple-Negative Breast Cancer for Improved Response to PLK1 Therapeutics

2021 ◽  
Vol 1 (3) ◽  
pp. 178-193
Author(s):  
Yang Gao ◽  
Elena B. Kabotyanski ◽  
Jonathan H. Shepherd ◽  
Elizabeth Villegas ◽  
Deanna Acosta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Null Mouse ◽  
Chromosome 5Q ◽  
Basal Like Breast Cancer ◽  
Cycle Regulation

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 patient-derived xenograft (PDX) TNBC models using the PLK1 inhibitor volasertib alone or in combination with carboplatin. Reexpression 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. Significance: The tumor-suppressive role of PLK2, and its relationship with oncogene PLK1, provide a mechanistic rationalization to use PLK1 inhibitors in combination with chemotherapy to treat PLK2-low/deleted tumors. TNBC, and other cancers with low PLK2 expression, are such candidates to leverage precision medicine to identify patients who might benefit from treatment with these inhibitors.

Sign in / Sign up

Export Citation Format

Share Document