Reprogramming of retinoblastoma cancer cells into cancer stem cells

Yue, Fengming; Hirashima, Kanji; Tomotsune, Daihachiro; Takizawa-Shirasawa, Sakiko; Yokoyama, Tetsuji; Sasaki, Katsunori

doi:10.1016/j.bbrc.2016.11.072

Cited by 10 publications

(7 citation statements)

References 20 publications

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“…Somatic cells from patients with germline RB1 mutations have been used to generate iPSC lines with heterozygous RB1 deletion [ 103 , 104 , 105 ]. However, neither iPSCs with subsequent inactivation of the other RB1 allele nor retinal organoids derived from RB1 -deficient iPSCs have been reported.…”

Section: Disease Modelingmentioning

confidence: 99%

Retinoblastoma: Etiology, Modeling, and Treatment

Kaewkhaw

Rojanaporn

2020

Cancers

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Retinoblastoma is a retinal cancer that is initiated in response to biallelic loss of RB1 in almost all cases, together with other genetic/epigenetic changes culminating in the development of cancer. RB1 deficiency makes the retinoblastoma cell-of-origin extremely susceptible to cancerous transformation, and the tumor cell-of-origin appears to depend on the developmental stage and species. These are important to establish reliable preclinical models to study the disease and develop therapies. Although retinoblastoma is the most curable pediatric cancer with a high survival rate, advanced tumors limit globe salvage and are often associated with high-risk histopathological features predictive of dissemination. The advent of chemotherapy has improved treatment outcomes, which is effective for globe preservation with new routes of targeted drug delivery. However, molecularly targeted therapeutics with more effectiveness and less toxicity are needed. Here, we review the current knowledge concerning retinoblastoma genesis with particular attention to the genomic and transcriptomic landscapes with correlations to clinicopathological characteristics, as well as the retinoblastoma cell-of-origin and current disease models. We further discuss current treatments, clinicopathological correlations, which assist in guiding treatment and may facilitate globe preservation, and finally we discuss targeted therapeutics for future treatments.

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Section: Disease Modelingmentioning

confidence: 99%

Retinoblastoma: Etiology, Modeling, and Treatment

Kaewkhaw

Rojanaporn

2020

Cancers

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“…FOXM1 has also been found to promote the proliferation and maintenance of pancreatic, breast and lung cancer stem cells [99], [102], [103], [104], [105], and its depletion represses the stemness of these cancer cells. Oct4, Sox2 and c-Myc are key factors involved in the reprogramming of cancer cells into cancer stem cells [106], [107]. FOXM1 has been shown to promote stem cell pluripotency by promoting the transcription of Oct4 (also called K15, POU5F1), which helps to suppress cellular differentiation [101].…”

Section: Chemotherapeutic Agents That Target Foxo3-foxm1mentioning

confidence: 99%

The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance

Yao

Fan

Lam

2018

Seminars in Cancer Biology

181

149

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The FOXO3 and FOXM1 forkhead box transcription factors, functioning downstream of the essential PI3K-Akt, Ras-ERK and JNK/p38MAPK signalling cascades, are crucial for cell proliferation, differentiation, cell survival, senescence, DNA damage repair and cell cycle control. The development of resistance to both conventional and newly emerged molecularly targeted therapies is a major challenge confronting current cancer treatment in the clinic. Intriguingly, the mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to molecularly targeted therapies are invariably linked to deregulated signalling through the FOXO3 and FOXM1 transcription factors. This is owing to the involvement of FOXO3 and FOXM1 in the regulation of genes linked to crucial drug action-related cellular processes, including stem cell renewal, DNA repair, cell survival, drug efflux, and deregulated mitosis. A better understanding of the mechanisms regulating the FOXO3-FOXM1 axis, as well as their downstream transcriptional targets and functions, may render these proteins reliable and early diagnostic/prognostic factors as well as crucial therapeutic targets for cancer treatment and importantly, for overcoming chemotherapeutic drug resistance.

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“…As shown in Figure 2A, 5-FU suppressed the tumorsphere formation of PANC-1 cells in a concentration-dependent manner, as demonstrated by the decrease of the mean diameter of 20 tumorspheres. In addition, CD44 and CD133 are specific biomarkers of CSCs [21]. Flow cytometry was performed to evaluate the proportion of CD44+CD133+ cells, in turn determining the proportion of CSCs in PANC-1 cells…”

Section: Effect Of 5-fu On the Stemness Maintenance Of Panc-1 Cellsmentioning

confidence: 99%