ABCG2 is required for self-renewal and chemoresistance of CD133-positive human colorectal cancer cells

Ma, Lijun; Liu, Ting; Jin, Yiran; Wei, Jun; Yang, Yinxue; Zhang, Hongquan

doi:10.1007/s13277-016-5209-5

Cited by 39 publications

(26 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug resistance was originally attributed to drug efflux mediated by adenosine triphosphate-binding cassette transporter (8,9). Increasing evidence has indicated the existence of cancer stem cells (CSCs) in breast cancer, and these CSCs are involved in the process of cancer initiation, metastasis, recurrence and therapeutic resistance (3,6,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). CSCs have cancer-initiating capability and metastatic potential (4,(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066

et al. 2018

View full text Add to dashboard Cite

Doxorubicin (Dox) is widely used in the treatment of triple-negative breast cancer cells (TNBCs), however resistance limits its effectiveness. Cancer stem cells (CSCs) are associated with Dox resistance in MCF-7 estrogen receptor positive breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) may functionally shift non-CSCs towards CSCs. However, whether Stat3 drives the formation of CSCs during the development of resistance in TNBC, and whether a Stat3 inhibitor reverses CSC-mediated Dox resistance, remains to be elucidated. In the present study, human MDA-MB-468 and murine 4T1 mammary carcinoma cell lines with the typical characteristics of TNBCs, were compared with estrogen receptor-positive MCF-7 cells as a model system. The MTT assay was used to detect cytotoxicity of Dox. In addition, the expression levels of CSC-specific markers and transcriptional factors were measured by western blotting, immunofluorescence staining and flow cytometry. The mammosphere formation assay was used to detect stem cell activity. Under long-term continuous treatment with Dox at a low concentration, TNBC cultures not only exhibited a drug-resistant phenotype, but also showed CSC properties. These Dox-resistant TNBC cells showed activation of Stat3 and high expression levels of pluripotency transcription factors octamer-binding transcription factor-4 (Oct-4) and c-Myc, which was different from the high expression of superoxide dismutase 2 (Sox2) in Dox-resistant MCF-7 cells. WP1066 inhibited the phosphorylation of Stat3, and decreased the expression of Oct-4 and c-Myc, leading to a reduction in the CD44-positive cell population, and restoring the sensitivity of the cells to Dox. Taken together, a novel signal circuit of Stat3/Oct-4/c-Myc was identified for regulating stemness-mediated Dox resistance in TNBC. The Stat3 inhibitor WP1066 was able to overcome the resistance to Dox through decreasing the enrichment of CSCs, highlighting the therapeutic potential of WP1066 as a novel sensitizer of Dox-resistant TNBC.

show abstract

Section: Introductionmentioning

confidence: 99%

Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The major mechanism of MDR in human cancer is the upregulation of ATP‐dependent drug efflux pumps by ATP‐binding cassette (ABC) transporters, such as P‐glycoprotein (P‐gp) (P‐gp/MDR1 [multidrug resistance 1]/ABCB1), multidrug resistance protein 1 (MRP1) (MRP1/ABCC1), and breast cancer resistance protein (BCRP) (BCRP/MXR [mitoxantrone resistance]/ABCP/ABCG2) . ABCG2 is highly expressed in the blood–brain barrier (BBB) and gastrointestinal tract and plays a role in protection against xenobiotic exposure .…”

Section: Introductionmentioning

confidence: 99%

Lupeol alters ER stress‐signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin‐resistant LoVo colorectal cancer cell apoptosis

Chen

Hsu

Chu

et al. 2018

Environmental Toxicology

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death. There are several first-line chemotherapeutic drugs used to treat CRC. Oxaliplatin (OXA) is an alkylating cytotoxic agent that is usually combined with other chemotherapeutic drugs to treat stage II and stage III CRC. However, cancer cells commonly acquire multidrug resistance (MDR), which is a major obstruction to cancer treatment. Recent studies have shown that natural components from traditional Chinese medicine or foods that have many biological functions may be new adjuvant therapies in clinical trials. We challenged LoVo CRC cell lines with OXA in a dose-dependent manner to create an OXA-resistant model. The expression of ABCG2 was significantly higher, and levels of endoplasmic reticulum (ER) stress markers were lower than those Parental cells. However, Lupeol, which is found in fruits and vegetables, has been shown to have bioactive properties, including anti-tumor properties that are relevant to many diseases. In our study, Lupeol downregulated cell viability and activated cell apoptosis. Moreover, Lupeol decreased the expression of ABCG2 and activated ER stress to induce OXA-resistant cell death. Importantly, the anti-tumor effect of Lupeol in OXA-resistant cells was higher than that of LoVo Parental cells. In addition, we also confirmed our results with a xenograft animal model, and the tumor size significantly decreased after Lupeol injections. Our findings show that Lupeol served as a strong chemoresistant sensitizer and could be a new adjuvant therapy method for chemoresistant patients.

show abstract

“…For example, in colorectal cancer it has been shown that the down regulation of ABCG2 inhibited the self-renewal capacity of these cells, enhancing the efficacy of chemotherapic-induced apoptosis [66]. High levels of ABCG2 was found associated to CSC-like phenotype in human melanoma [21].…”

Section: Limitation Of Current Therapies For Metastasismentioning

confidence: 99%

Complexity in cancer stem cells and tumor evolution: Toward precision medicine

Porta

Zapperi

2017

Seminars in Cancer Biology

View full text Add to dashboard Cite

In this review, we discuss recent advances on the plasticity of cancer stem cells and highlight their relevance to understand the metastatic process and to guide therapeutic interventions. Recent results suggest that the strict hierarchical structure of cancer cell populations advocated by the cancer stem cell model must be reconsidered since the depletion of cancer stem cells leads the other tumor cells to switch back into the cancer stem cell phenotype. This plasticity has important implications for metastasis since migrating cells do not need to be cancer stem cells in order to seed a metastasis. We also discuss the important role of the immune system and the microenvironment in modulating phenotypic switching and suggest possible avenues to exploit our understanding of this process to develop an effective strategy for precision medicine.

show abstract

ABCG2 is required for self-renewal and chemoresistance of CD133-positive human colorectal cancer cells

Cited by 39 publications

References 21 publications

Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066

Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066

Lupeol alters ER stress‐signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin‐resistant LoVo colorectal cancer cell apoptosis

Complexity in cancer stem cells and tumor evolution: Toward precision medicine

Contact Info

Product

Resources

About