STAT3 as a promising chemoresistance biomarker associated with the CD44 +/high /CD24 -/low /ALDH + BCSCs-like subset of the triple-negative breast cancer (TNBC) cell line

Moreira, Milene Pereira; Braga, Letícia da Conceição; Cassali, Geovanni Dantas; Silva, Luciana Maria

doi:10.1016/j.yexcr.2018.01.018

Cited by 44 publications

(27 citation statements)

References 65 publications

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“…Src silenced MDA-MB-231 cells showed low protein levels of STAT3 and AKT proposing that Src/AKT/STAT3 signaling pathway play a role in chemoresistance [ 149 ]. These results are consistent with Moreira et al findings that confirmed overexpression of STAT3 protein in doxorubicin-treated TNBC BT-549 cells suggesting that STAT3 is an essential EGF gene involved in doxorubicin-based resistance [ 150 ].…”

Section: Pre-clinical Activity Of Engineered Sirna-mediated Therapsupporting

confidence: 93%

Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements

Hattab

Bakhtiar

2020

Pharmaceutics

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Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer. Owing to the absenteeism of hormonal receptors expressed at the cancerous breast cells, hormonal therapies and other medications targeting human epidermal growth factor receptor 2 (HER2) are ineffective in TNBC patients, making traditional chemotherapeutic agents the only current appropriate regimen. Patients’ predisposition to relapse and metastasis, chemotherapeutics’ cytotoxicity and resistance and poor prognosis of TNBC necessitates researchers to investigate different novel-targeted therapeutics. The role of small interfering RNA (siRNA) in silencing the genes/proteins that are aberrantly overexpressed in carcinoma cells showed great potential as part of TNBC therapeutic regimen. However, targeting specificity, siRNA stability, and delivery efficiency cause challenges in the progression of this application clinically. Nanotechnology was highlighted as a promising approach for encapsulating and transporting siRNA with high efficiency-low toxicity profile. Advances in preclinical and clinical studies utilizing engineered siRNA-loaded nanotherapeutics for treatment of TNBC were discussed. Specific and selective targeting of diverse signaling molecules/pathways at the level of tumor proliferation and cell cycle, tumor invasion and metastasis, angiogenesis and tumor microenvironment, and chemotherapeutics’ resistance demonstrated greater activity via integration of siRNA-complexed nanoparticles.

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Section: Pre-clinical Activity Of Engineered Sirna-mediated Therapsupporting

confidence: 93%

Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements

Hattab

Bakhtiar

2020

Pharmaceutics

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“…STAT3 has been shown to be highly involved in the development and progression of BCSCs and might be a chemoresistance biomarker associated with BCSCs [ 8 , 9 , 58 ]. BCSCs can be identified and isolated by their markers: CD44 + /CD24 – and increased aldehyde dehydrogenase 1 (ALDH1) activity [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

Ganoderma lucidumextract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

et al. 2018

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The aggressive nature of triple negative breast cancer (TNBC) may be explained in part by the presence of breast cancer stem cells (BCSCs), a subpopulation of cells, which are involved in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The signal transducer and activator of transcription 3 (STAT3) pathway participates in the development and progression of BCSCs, but its role in TNBC remains unclear. Here, we report that Ganoderma lucidum extract (GLE), a medicinal mushroom with anticancer activity, acts on BCSCs in vitro and in TNBC pre-clinical animal tumor models by downregulating the STAT3 pathway. We show that GLE significantly reduces TNBC cell viability, and down-regulates total and phosphorylated STAT3 expression. This is consistent with the reduction of OCT4, NANOG and SOX2 expression, reduction in the BCSC population by loss of the ALDH1 and CD44+/CD24– population, the deformation of mammospheres, and the strong reduction in animal tumor volume and tumor weight. Analysis of the BCSC compartment in tumors revealed that GLE decreases the STAT3 pathway and the expression of OCT4, NANOG, and SOX2 in BCSCs. These findings demonstrate that the anti-cancer activity of GLE targets BCSCs of TNBC through the downregulation of the STAT3 pathway.

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“…IL‐6 was involved in TNBC cell growth, survival, migration, metastasis and stemness . As a downstream intracellular molecule of IL‐6, Stat3 was also overactivated in TNBC, and associated with the aggressive phenotype . Targeting IL‐6/Stat3 was demonstrated to suppress breast cancer growth and metastasis in mouse xenograft models .…”

Section: Discussionmentioning

confidence: 99%

CD155 contributes to the mesenchymal phenotype of triple‐negative breast cancer

et al. 2020

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Patients with triple‐negative breast cancer (TNBC) lack molecular targets and have an unfavorable outcome. CD155 is overexpressed in human cancers, but whether it plays a role in TNBC is unexplored. Here we found that CD155 was enriched in both TNBC cell lines and tumor tissues. High CD155 expression was related to poor prognosis of breast cancer patients. CD155 was associated with a mesenchymal phenotype. CD155 knockdown induced a mesenchymal‐epithelial transition in TNBC cells, and suppressed TNBC cell migration, invasion and metastasis in vitro and in vivo. Mechanistically, CD155 cross‐talked with oncogenic IL‐6/Stat3 and TGF‐β/Smad3 pathways. Moreover, CD155 knockdown inhibited TNBC cell growth and survival. Taken together, these data indicate that CD155 contributes to the aggressive behavior of TNBC; targeting CD155 may be beneficial to these patients.

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STAT3 as a promising chemoresistance biomarker associated with the CD44 +/high /CD24 -/low /ALDH + BCSCs-like subset of the triple-negative breast cancer (TNBC) cell line

Cited by 44 publications

References 65 publications

Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements

Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements

Ganoderma lucidumextract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

CD155 contributes to the mesenchymal phenotype of triple‐negative breast cancer

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