Cancer stem cells as functional biomarkers

Lee

et al. 2020

Preprint

Cancer stem cells (CSCs) are regarded as essential targets to overcome tumor progression and therapeutic resistance; however, practical targeting approaches are limited. Here, we identify testis-specific Y-like protein 5 (TSPYL5) as a CSC-associated factor that promotes stemness and epithelial-to-mesenchymal transition in therapy-resistant non-small cell lung cancer (NSCLC) cells. Aberrantly activated PI3K/AKT pathway in therapy-resistant NSCLC cells promotes TSPYL5 phosphorylation at threonine-120 (pT120), which inhibits ubiquitination and stabilizes TSPYL5. TSPYL5 pT120 also supports SUMOylation, which leads to its nuclear translocation and functions as a transcriptional repressor of PTEN. Nuclear TSPYL5 also activates the transcription of CSC-associated genes, ALDH1 and CD44. Collectively, TSPYL5 pT120 maintains persistent CSC-like characteristics via transcriptional activation of CSC-associated genes and via a positive-feedback loop between the AKT/TSPYL5/PTEN and PTEN/PI3K/AKT signaling pathways. However, inhibition of TSPYL5 pT120 can block aberrant AKT/TSPYL5/PTEN cyclic signaling and cancer stemness. Our study suggests TSPYL5 as a novel target for cancer therapy.

“…So far, intensive research has been conducted to identify and target CSCs using speci c marker subsets 22 . Nevertheless, the targeted elimination of CSCs remains a challenge.…”

Section: Introductionmentioning

confidence: 99%

Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

Lee

et al. 2020

Preprint

“…Despite advances in the prevention, diagnosis, and treatment of CRC, effective treatment strategies for this disease have yet to be developed 3. Metastasis and relapse are the main causes of failure in the treatment of CRC 4. Therefore, elucidating the molecular mechanisms underlying CRC progression and metastasis is important.…”

Section: Introductionmentioning

confidence: 99%

Regulation Mechanism of Long Noncoding RNAs in Colon Cancer Development and Progression

et al. 2019

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and its high rates of relapse and metastasis are associated with a poor prognosis. Despite extensive research, the underlying regulatory mechanisms of CRC remain unclear. Long noncoding RNAs (lncRNAs) are a major type of noncoding RNAs that have received increasing attention in the past few years, and studies have shown that they play a role in many biological processes in CRC. Here, we summarize recent studies on lncRNAs associated with CRC and the signaling pathways and mechanisms underlying this association. We show that dysregulated lncRNAs may be new prognostic and diagnostic biomarkers or therapeutic targets for clinical application. This review contributes not only to our understanding of CRC, but also suggests novel signaling pathways associated with lncRNAs that can be targeted to block or eradicate CRC.

BioMed Research International

“…Similar to most malignancies, liver cancer is composed of a heterogeneous cell hierarchy, in which a distinct small subset referred to as cancer stem cells (CSCs) resides [ 3 ]. CSCs have unlimited proliferation, self-renewal, differentiation, and tumor-regenerating capacities, which lead to tumor initiation, relapse, metastasis, and drug resistance [ 4 ]. Liver CSCs are the main obstacle to the cure for refractory liver cancer.…”

Section: Introductionmentioning

confidence: 99%

The Diverse Mechanisms of miRNAs and lncRNAs in the Maintenance of Liver Cancer Stem Cells

Zhao

et al. 2018

Liver cancer is the second leading cause of cancer-related death worldwide. The high frequency of recurrence and metastasis is the main reason for poor prognosis. Liver cancer stem cells (CSCs) have unlimited self-renewal, differentiation, and tumor-regenerating capacities. The maintenance of CSCs may account for the refractory features of liver cancer. Despite extensive investigations, the underlying regulatory mechanisms of liver CSCs remain elusive. miRNA and lncRNA, two major classes of the ncRNA family, can exert important roles in various biological processes, and their diverse regulatory mechanisms in CSC maintenance have acquired increasing attention. However, to the best of our knowledge, there is a lack of reviews summarizing these findings. Therefore, we systematically recapitulated the latest studies on miRNAs and lncRNAs in sustaining liver CSCs. Moreover, we highlighted the potential clinical application of these dysregulated ncRNAs as novel diagnostic and prognostic biomarkers and therapeutic targets. This review not only sheds new light to fully understand liver CSCs but also provides valuable clues on targeting ncRNAs to block or eradicate CSCs in cancer treatment.