PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer

Spasojevic, Caroline; Marangoni, Elisabetta; Vacher, Sophie; Assayag, Franck; Meseure, Didier; Château-Joubert, Sophie; Humbert, M.; Karam, Manale; Ricort, Jean Marc; Auclair, Christian; Regairaz, Marie; Bièche, Ivan

doi:10.18632/oncotarget.25292

Cited by 16 publications

(15 citation statements)

References 33 publications

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“…PRKD1 overexpression helps to maintain cancer stemness through phosphorylation of protein kinase D/protein kinase C (PKD/PKCµ) and activation of the Wnt/β-catenin pathway [50]. Additionally, phosphorylated PKD/PKCµ has a negative effect on apoptosis through caspase-3 inhibition [51].…”

Section: Mir-34amentioning

confidence: 99%

“…However, the specific mechanism of PRKD1 remains unknown [50], and some research also indicates that PRKD1 has a contrary effect as a tumor suppressor or promoter in different cancer types [53]. For example, PRKD1 is expressed in normal ductal epithelial cells of the breast and inhibits EMT, which is a vital step for tumor cells to acquire the ability of invasion and metastasis [54].…”

Section: Mir-34amentioning

confidence: 99%

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microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Jiao

Qian

et al. 2019

Cells

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Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.

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Section: Mir-34amentioning

confidence: 99%

Section: Mir-34amentioning

confidence: 99%

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Jiao

Qian

et al. 2019

Cells

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“…We previously demonstrated that PKD1 overexpression potentiates in vivo tumor growth of the MCF-7 adenocarcinoma-derived cell line, and regulates cell growth (Karam et al, 2012;Karam et al, 2014). Moreover, we identified PKD1 as a poor prognostic factor in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically (Spasojevic et al, 2018). Therefore, due to its crucial role in breast tumor growth and development, we asked in this study whether PKD1 may be a molecular target of BPA.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells

et al. 2020

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Exposure to bisphenol A (BPA), one of the most widespread endocrine disruptors present in our environment, has been associated with the recent increased prevalence and severity of several diseases such as diabetes, obesity, autism, reproductive and neurological defects, oral diseases, and cancers such as breast tumors. BPA is suspected to act through genomic and non-genomic pathways. However, its precise molecular mechanisms are still largely unknown. Our goal was to identify and characterize a new molecular target of BPA in breast cancer cells in order to better understand how this compound may affect breast tumor growth and development. By using in vitro (MCF-7, T47D, Hs578t, and MDA-MB231 cell lines) and in vivo models, we demonstrated that PKD1 is a functional non-genomic target of BPA. PKD1 specifically mediates BPAinduced cell proliferation, clonogenicity, and anchorage-independent growth of breast tumor cells. Additionally, low-doses of BPA (≤10 −8 M) induced the phosphorylation of PKD1, a key signature of its activation state. Moreover, PKD1 overexpression increased the growth of BPA-exposed breast tumor xenografts in vivo in athymic female Swiss nude (Foxn1 nu/nu ) mice. These findings further our understanding of the molecular mechanisms of BPA. By defining PKD1 as a functional target of BPA in breast cancer cell proliferation and tumor development, they provide new insights into the pathogenesis related to the exposure to BPA and other endocrine disruptors acting similarly.

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“… 6 - 8 Moreover, the previous study suggests that elevated tumor PKD1 expression independently predicts worse prognosis in patients with cancer. 9 Considering the regulation of PKD1 in the malignant progression of NSCLC, and its role as a biomarker in patients with cancer, we hypothesized that PKD1 might act as a potential biomarker in NSCLC. However, the clinical application of PKD1 in NSCLC largely remains to be discovered.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase D1 Is Increased in Tumor Tissue, Correlates With Advanced Tumor Features and Worse Prognosis of Non-Small Cell Lung Cancer

Yao

Jiang

Geng

et al. 2020

Technol Cancer Res Treat

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Objective: This study aimed to assess protein kinase D1 expression and its association with tumor characteristics as well as prognosis in patients with non-small cell lung cancer. Methods: Protein kinase D1 expression in tumor tissues and adjacent tissues from 172 patients with non-small cell lung cancer who underwent surgical resection were analyzed by immunohistochemical staining. Based on the total immunohistochemical score, protein kinase D1 expression was classified as protein kinase D1 high expression (further divided into protein kinase D1 high+++, protein kinase D1 high++, and protein kinase D1 high+ expressions) and protein kinase D1 low expression. Clinical characteristics of patients with non-small cell lung cancer were acquired from the database. Accumulating disease-free survival and overall survival were calculated based on patients’ relapse/survival status. Results: Protein kinase D1 expression was increased in tumor tissues compared to adjacent tissues ( P < .001). Tumor protein kinase D1 high expression correlated with poorer pathological differentiation ( P = .041), increased tumor size ( P = .003), the presence of lymph node metastasis ( P = .001), and elevated tumor, nodes and metastases stage ( P < .001). Besides, both accumulating disease-free survival and overall survival were decreased in patients with tumor protein kinase D1 high expression compared to patients with tumor protein kinase D1 low expression ( P = .010 for disease-free survival and P = 0.005 for overall survival). Moreover, they were lowest in patients with tumor protein kinase D1 high+++ expression, followed by patients with tumor protein kinase D1 high++ expression, then patients with tumor protein kinase D1 high+ expression, and highest in patients with tumor protein kinase D1 low expression ( P < .001 for disease-free survival and P = .001 for overall survival). Notably, higher tumor protein kinase D1 expression was an independent predictive factor for decreased disease-free survival ( P = .001) and overall survival ( P = .004). Conclusions: Protein kinase D1 might be a potential marker to identify patients with non-small cell lung cancer with worse tumor features and prognosis.

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PKD1 is a potential biomarker and therapeutic target in triple-negative breast cancer

Cited by 16 publications

References 33 publications

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells

Protein Kinase D1 Is Increased in Tumor Tissue, Correlates With Advanced Tumor Features and Worse Prognosis of Non-Small Cell Lung Cancer

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