The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

Tandon, Manish; Othman, Ahmad; Ashok, Vivek; Stein, Gary S.; Pratap, Jitesh

doi:10.1002/jcp.25916

Cited by 35 publications

(48 citation statements)

References 73 publications

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“…Given their importance for autophagosome formation, both often are used as indicators of autophagy. [48,49,53,54] The genes that encode these proteins, as well as others critical in autophagy (ULK1 and ULK2 indicative of induction, p62/SQSTM1 indicative of autophagosome formation), were among those observed by RNA-seq to have significantly increased expression in dormant ER+ T47D cells within our bioinspired 3D culture system.…”

Section: Expression Of Markers Of Autophagy In the Er+ Breast Cancer mentioning

confidence: 89%

“…[45][46][47] Autophagy is the process where cells degrade and recycle cellular components, by formation of an autophagosome, to maintain activity and viability when under stress, and the HADb is a public repository that provides a complete "list of human genes and proteins involved directly or indirectly in autophagy as described in literature" (http://autophagy.lu/index.html). [48,49] While autophagy has been implicated in cancer for decades, autophagy more recently has been reported as a survival mechanism for dormant cancer cells and breast cancer stem cells. [50][51][52] As autophagy is a multi-step process, including induction, phagophore formation, elongation and autophagosome formation, lysosomal fusion, and degradation, we examined two specific proteins important in different autophagy steps, ATG9B and microtubule associated protein 1 light chain 3 beta (MAP1LC3B) (LC3B), for probing autophagy within the 3D ER+ dormancy model.…”

Section: Expression Of Markers Of Autophagy In the Er+ Breast Cancer mentioning

confidence: 99%

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Understanding ER+ Breast Cancer Dormancy Using Bioinspired Synthetic Matrices for Long‐Term 3D Culture and Insights into Late Recurrence

et al. 2020

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Late recurrences of breast cancer are hypothesized to originate from disseminated tumor cells that re‐activate after a long period of dormancy, ≥5 years for estrogen‐receptor positive (ER+) tumors. An outstanding question remains as to what the key microenvironment interactions are that regulate this complex process, and well‐defined human model systems are needed for probing this. Here, a robust, bioinspired 3D ER+ dormancy culture model is established and utilized to probe the effects of matrix properties for common sites of late recurrence on breast cancer cell dormancy. Formation of dormant micrometastases over several weeks is examined for ER+ cells (T47D, BT474), where the timing of entry into dormancy versus persistent growth depends on matrix composition and cell type. In contrast, triple negative cells (MDA‐MB‐231), associated with early recurrence, are not observed to undergo long‐term dormancy. Bioinformatic analyses quantitatively support an increased “dormancy score” gene signature for ER+ cells (T47D) and reveal differential expression of genes associated with different biological processes based on matrix composition. Further, these analyses support a link between dormancy and autophagy, a potential survival mechanism. This robust model system will allow systematic investigations of other cell‐microenvironment interactions in dormancy and evaluation of therapeutics for preventing late recurrence.

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Section: Expression Of Markers Of Autophagy In the Er+ Breast Cancer mentioning

confidence: 89%

Section: Expression Of Markers Of Autophagy In the Er+ Breast Cancer mentioning

confidence: 99%

Understanding ER+ Breast Cancer Dormancy Using Bioinspired Synthetic Matrices for Long‐Term 3D Culture and Insights into Late Recurrence

et al. 2020

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“…It acts as a scaffold for nucleic acids and regulatory factors involved in osteoblastic differentiation and skeletal morphogenesis (13)(14)(15). It was recently revealed that RUNX2 can promote breast cancer cell survival under metabolic stress, as well as bone metastases (16,17). Furthermore, the targeting of RUNX2 by miR-135 and miR-203 impairs breast cancer progression and distant metastasis (18).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑153 inhibits cell proliferation, migration, invasion and epithelial‑mesenchymal transition in breast cancer via direct targeting of RUNX2

Zuo

Liu

et al. 2019

Exp Ther Med

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A number of microRNAs (miRNAs) are involved in the development and malignant progression of numerous types of human cancer including breast cancer. The underlying regulatory mechanism of miRNA-153 (miR-153) in breast cancer progression remains largely unknown. The present study demonstrated that miR-153 expression levels were significantly reduced in breast cancer tissue samples and cell lines, compared with adjacent healthy tissue samples and normal human breast cell line MCF-10A. In addition, low miR-153 expression was associated with advanced clinical staging and metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Furthermore, patients with breast cancer with low miR-153 expression had poor prognosis, compared with patients with breast cancer with high miR-153 expression. Overexpression of miR-153 reduced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in breast cancer SK-BR-3 and BT-549 cells. Runt-related transcription factor 2 (RUNX2), which was revealed to be significantly upregulated in breast cancer, was verified as a target gene of miR-153 in SK-BR-3 and BT-549 cells by luciferase reporter gene assay. High RUNX2 expression was associated with advanced clinical staging as well as distant and lymph node metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Additionally, an inverse correlation between miR-153 and RUNX2 mRNA expression levels was observed in breast cancer tissues. RUNX2 overexpression reduced the suppressive effects of miR-153 on the proliferation, migration, invasion and EMT of SK-BR-3 and BT-549 cells. The present study indicated that miR-153 may serve a role in breast tumor growth and metastasis via direct targeting of RUNX2. The miR-153/RUNX2 axis may be used as a potential therapeutic target in breast cancer treatment.

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“…Numerous studies have demonstrated that RUNX2 participates in the physiological and pathological processes of various diseases, such as cancers [43][44][45], asthma [46], cleidocranial dysplasia [47,48], and acromegaly [49]. Many studies have also verified that RUNX2 expression is closely associated with the progression of various diseases by affecting cell proliferation, apoptosis, autophagy, metastasis, and osteogenic differentiation [50][51][52]. However, its function in RPE cells has remained unknown.…”

Section: Discussionmentioning

confidence: 99%

Glucose-induced microRNA-218 suppresses the proliferation and promotes the apoptosis of human retinal pigment epithelium cells by targeting RUNX2

Yao

Liu

et al. 2019

Bioscience Reports

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Objective: MicroRNA-218 (miR-218) critical for preventing the progression of numerous diseases, including diseases of the retinal pigment epithelium (RPE). However, the mechanism by which miR-218 regulates the PRE in humans remains largely unknown. Our study investigated the effects of glucose-induced miR-218 expression on human RPE cells (ARPE-19), as well as its targeted regulatory effect. Methods: The levels of miR-218 and runt-related transcription factor 2 (RUNX2) expression were investigated by RT-qPCR or Western blot assays. Cell viability and apoptosis were assessed by CCK-8 assays, flow cytometry, and Hoechst staining. A luciferase reporter assay was performed to determine whether Runx2 is a target gene of miR-218. Results: Our results showed that glucose up-regulated miR-218 expression, suppressed proliferation, and induced the apoptosis of ARPE-19 cells. We verified that miR-218 could inhibit the proliferation and facilitate the apoptosis of ARPE-19 cells, while inhibition of miR-218 expression produced the opposite effects. In terms of mechanism, we demonstrated that RUNX2 was a direct target of miR-218. Functional experiments showed that Runx2 served as a miR-218 target to help inhibit the proliferation and induction of apoptosis in ARPE-19 cells. Conclusion: Our findings suggest the miR-218/Runx2 axis as a potential target for treating diabetic retinopathy (DR).

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The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

Cited by 35 publications

References 73 publications

Understanding ER+ Breast Cancer Dormancy Using Bioinspired Synthetic Matrices for Long‐Term 3D Culture and Insights into Late Recurrence

Understanding ER+ Breast Cancer Dormancy Using Bioinspired Synthetic Matrices for Long‐Term 3D Culture and Insights into Late Recurrence

MicroRNA‑153 inhibits cell proliferation, migration, invasion and epithelial‑mesenchymal transition in breast cancer via direct targeting of RUNX2

Glucose-induced microRNA-218 suppresses the proliferation and promotes the apoptosis of human retinal pigment epithelium cells by targeting RUNX2

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