Molecular aspects of breast cancer resistance to drugs (Review)

Calaf, Gloria M.; Zepeda, Andrea B.; Castillo, Rodrigo; Figueroa, Carolina A.; Arias, Consuelo; Figueroa, Elías; Farías, Jorge G.

doi:10.3892/ijo.2015.3055

Cited by 24 publications

(20 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of patients are at advanced stages at the time of diagnosis, and the prognosis of these patients remains poor (2). Currently, adjuvant chemotherapy and radiotherapy following surgical resection is the most commonly used treatment strategy, however, the 5-year survival rate of breast cancer remains low, and the improvement of prognosis of breast cancer patients has reached a plateau (3,4). Therefore, finding promising therapeutic and prognostic targets is essential for developing effective therapies for breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA‑MTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis

et al. 2018

View full text Add to dashboard Cite

Circular RNAs (circRNAs), a class of endogenous RNAs, have emerged as an enigmatic class of genes. However, little is known about their value in the progression and chemoresistance of cancers. The present study sought to determine the expression profiles and potential modulatory role of circRNAs on breast cancer cell viability and monastrol resistance. Monastrol-resistant cell lines were established by exposing breast cancer cells to increasing concentrations of monastrol. A human circRNA microarray was used to search for dysregulated circRNAs in monastrol-resistant cells, then circRNA‑MTO1 (hsa‑circRNA-007874) was validated as a circRNA that exhibited elevated expression levels in monastrol-resistant cells. Mechanistic investigations suggested that upregulation of circRNA‑MTO1 suppressed cell viability, promoted monastrol-induced cell cytotoxicity and reversed monastrol resistance. Subsequently, Eg5 was identified as the functional target of circRNA‑MTO1, and MTO1 inhibited Eg5 protein level but not mRNA level. By treating with protein synthesis inhibitor cycloheximide (CHX), it was revealed that MTO1 did not affect the protein stability of Eg5. RNA-pull down experiments followed by mass spectrometry revealed that MTO1 interacted with tumor necrosis factor receptor associated factor 4 (TRAF4), and sequester TRAF4 from activating Eg5 translation, thereby inhibiting the Eg5 protein level. Taken together, the data reveal a regulatory mechanism by circRNA‑MTO1 to control cell viability and monastrol resistance in breast cancer cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Circular RNA‑MTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…However, outcomes are still unsatisfactory due to side effects, drug resistance, recurrence, and metastasis. Cancer cells are heterogeneous, versatile, and adaptable, leading to primary and secondary resistance (1). Side effects induced by systemic administration of cytotoxic anticancer drugs can produce serious clinical problems (2).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Cancer Immunotherapy with Smad3-Silenced NK-92 Cells

Wang

Tang

Lian

et al. 2018

Cancer Immunology Research

View full text Add to dashboard Cite

Natural killer (NK) cells, early effectors in anticancer immunity, are paralyzed by TGFβ1, an immunosuppressive cytokine produced by cancer cells. Development and activity of NK cells are largely inhibited in the Smad3-dependent tumor microenvironment. Here, we used genetic engineering to generate a stable SMAD3-silencing human NK cell line, NK-92-S3KD, whose cancer-killing activity and cytokine production were significantly enhanced under TGFβ1-rich condition compared with the parental cell line. Interestingly, we identified that the IFNG gene is a direct E4BP4 target gene. Thus, silencing of SMAD3 allows upregulation of E4BP4 that subsequently promoting interferon-γ (IFNγ) production in the NK-92-S3KD cells. More importantly, NK-92-S3KD immunotherapy increases the production of not only IFNγ, but also granzyme B and perforin in tumors; therefore, inhibiting cancer progression in two xenograft mouse models with human hepatoma (HepG2) and melanoma (A375). Thus, the NK-92-S3KD cell line may be useful for the clinical immunotherapy of cancer. .

show abstract

“…MED23 participates in formation of drug resistance of everolimus through mutual regulation with HER2 (25). The present study demonstrates that MED23 participates in the drug resistance of everolimus in endocrinotherapy, and explains that MED23 plays an extensive role in the regulation of the resistance of different types of endocrinotherapy drugs in breast cancer, and suggests that MED23 can function as a potential therapeutic target (sole or combined) to overcome the drug resistance of endocrinotherapy (26). …”

Section: Discussionmentioning

confidence: 51%

MED23 in endocrinotherapy for breast cancer

Lin

Zhang

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

We investigated the role of the transcriptional mediator subunit 23 (MED23) in everolimus drug resistance, invasion and metastasis during breast cancer treatment and its molecular mechanism. We also evaluated the endocrinotherapy and prevention method for breast cancer. Breast cancer cell strains were established that can continuously express MED23, as well as inducible MED23-shRNA expression plasmids. The inductive agent, doxycycline (Dox), was added to the water for long-term silencing of MED23 in intratumoral cells. We conducted experiments on the role of MED23 in the regulation of invasion and metastasis of breast cancer using cell culture, western blotting, MTT proliferation experiment, fluorescent quantitative PCR and chromatin immunoprecipitation (ChIP). The silencing of MED23 significantly inhibited cellular growth and proliferation as well as soft agar cloning. Silencing of MED23 strengthened the sensitivity of the everolimus-resistant breast cancer cell strains BT474 and MCF-7/ADM cells to everolimus medication. The silencing of MED23, in combination with everolimus, inhibits the cell cycle progress of breast cancer cells. ChIP indicated that the mutual regulation of HER2 and MED23 also participates in the formation of the everolimus drug resistance mechanism. Therefore, MED23 plays an important role in everolimus drug resistance, invasion, and metastasis of breast cancer. As a potential molecular therapeutic target of breast cancer, MED23 overcomes drug resistance in clinical endocrinotherapy and controls the distal relapse and metastasis in breast cancer by the targeted silencing of MED23.

show abstract

Molecular aspects of breast cancer resistance to drugs (Review)

Cited by 24 publications

References 59 publications

Circular RNA‑MTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis

Circular RNA‑MTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis

Enhanced Cancer Immunotherapy with Smad3-Silenced NK-92 Cells

MED23 in endocrinotherapy for breast cancer

Contact Info

Product

Resources

About