Therapeutic strategies against cancer stem cells in human colorectal cancer (Review)

Szaryńska, Magdalena; Olejniczak, Agata; Spychalski, Piotr; Kmieć, Zbigniew

doi:10.3892/ol.2017.7261

Cited by 31 publications

(36 citation statements)

References 178 publications

(222 reference statements)

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“…Colorectal cancer (CRC) is a leading cause of cancerrelated death [1,2]. Initial treatment is often surgical in nature, but because the disease is often not diagnosed until a more advanced and aggressive stage the application of chemotherapeutic agents is often essential to disease treatment [3,4]. There is a wide range of heterogeneity between colon cancer types, with nearly 30% of cases stemming from hereditary mutations and the remainder arising from de novo acquired mutations [5,6].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway

Yang

Zhang

et al. 2019

Cancer Gene Ther

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Cabozantinib is a multi-kinase inhibitor targeting MET, AXL, and VEGFR2, and has been approved for use in multiple malignancies. The means by which Cabozantinib acts to target colorectal cancer (CRC) cells remains poorly understood, and we sought to investigate how this drug disrupts cell growth in CRC cells and how it interacts to enhance the efficacy of other chemotherapeutic agents. In this study, we found that Cabozantinib activated a p65-dependent signaling pathway in response to both inhibition of AKT and activation of glycogen synthase kinase 3β (GSK3β), leading to upregulation of PUMA in CRC cells regardless of p53 activity. PUMA upregulation facilitates CRC apoptosis in response to Cabozantinib, which also acts synergistically with the chemotherapeutic agents Cetuximab and 5-FU to induce robust apoptosis in a PUMA-dependent manner. Eliminating PUMA expression ablated this apoptosis induced by Cabozantinib in xenograft mouse model. Our findings revealed that Cabozantinib acts to drive CRC cells apoptosis via a PUMA-dependent mechanism, thus identifying PUMA expression as a potential predictor of Cabozantinib efficacy and a potential novel therapeutic target.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway

Yang

Zhang

et al. 2019

Cancer Gene Ther

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“…Most studies isolated CRC‐CSC using FACS based on either the expression of cell surface proteins, for example CD133 and CD44, or ALDH activity . We have sorted PDX CRC cells using FACS based on higher expression of CD133, CD44, and higher ALDH activity and then subcutaneously implanted them into NOD‐SCID mice to test their tumorigenicity.…”

Section: Resultsmentioning

confidence: 99%

AMPK promotes the survival of colorectal cancer stem cells

Guo

Han

Tkach

et al. 2018

Anim Models and Exp Med

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Background Colorectal cancer ( CRC ) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis, chemotherapy resistance, and relapse. Methods To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient‐derived xenograft ( PDX ) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent‐activated cell sorting ( FACS ) and characterized their metabolic properties. Results Interestingly, we found that the CRC cancer stem cells (ie, CRC cells with higher ALDH activity, or ALDH +) express higher level of antioxidant genes and have lower level of reactive oxygen species ( ROS ) than non‐ CRC cancer stem cells (ie, CRC cells with lower ALDH activity, or ALDH−). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly, we observed higher AMP ‐activated protein kinase ( AMPK ) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem cells. Conclusion We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRC s.

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“…Characteristics of included studies are summarised in Table II. A study by Catalano et al focused on the role of THs in CRC stem cell differentiation and their sensitivity to chemotherapy [13]. CRC stem cells (CR-CSC) are a small group of cells with self-renewing potential and the ability to induce tumour growth [14,15]. CSCs are highly insensitive to chemotherapy and other kinds of treatment, which can lead to inefficient management of the disease [16].…”

Section: Cell Lines Studiesmentioning

confidence: 99%

Effects of thyroid hormone imbalance on colorectal cancer carcinogenesis and risk — a systematic review

Rostkowska

Spychalski

Dobrzycka

et al. 2019

Endokrynologia Polska

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Colorectal cancer (CRC) is the second leading cause of cancer-related death. The prevalence of colorectal neoplasm is increasing. Many studies have shown that thyroid dysfunction may be connected with the higher risk of pancreatic and breast cancer, but only a few described the role of thyroid dysfunction and thyroid hormone (TH) replacement in the development and risk of CRC. The aim of this study is to summarise all findings and potentially elucidate the connection between TH imbalance and colorectal cancer. The systematic review was conducted according to PICO and PRISMA guidelines. We searched MEDLINE, ClinicalTrials.gov, www.clinicaltrialsregister.eu, and Cochrane Library databases using the following keywords: "((((thyroid OR hypothyroidism OR hyperthyroidism OR levothyroxine OR hashimoto OR graves OR thyroidectomy)) AND (colon OR colorectal OR CRC)) NOT hashimoto[Author]) NOT graves[Author])". No filters were used. Of total of 3054 articles identified by the search strategy, 11 met PICO criteria and were included into the review. Four of those were on cell lines and seven were human studies. Analysis of the included studies revealed an elevated risk of CRC in patients with hypothyroidism with aORs ranging from 1.16 (95% CI: 1.08-1.24, p < 0.001) to 1.69 (95% CI: 1.21-2.36, p = 0.002). Moreover, TH replacement therapy has a protective effect for CRC risk with aOR ranging from 0.60 (95% CI: 0.44-0.81, p = 0.001) to 0.92 (95% CI: 0.86-0.98, p = 0.009). THs seem to play a role in colorectal carcinogenesis. Further studies are warranted to define the exact role of thyroid hormone imbalance in prevention and treatment of CRC. (Endokrynol Pol 2019; 70 (2): 190-197)

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Therapeutic strategies against cancer stem cells in human colorectal cancer (Review)

Cited by 31 publications

References 178 publications

RETRACTED ARTICLE: Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway

RETRACTED ARTICLE: Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway

AMPK promotes the survival of colorectal cancer stem cells

Effects of thyroid hormone imbalance on colorectal cancer carcinogenesis and risk — a systematic review

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