REC8 enhances stemness and promotes metastasis of colorectal cancer through BTK/Akt/β-catenin signaling pathway

Zhou, Xue; Xie, Xing; Liu, Ting; Chen, Shengxiong; Wang, Yijun; Zhang, Jiuna; Wang, Shuling; Wang, Yongjuan; Dou, Shiying; Qi, Ran; Kang, Ning; Zhang, Dongxuan; Jin, Xiaoxu; Cui, Ruolin; Jiang, Hui‐Qing

doi:10.1016/j.tranon.2021.101305

Cited by 8 publications

(1 citation statement)

References 31 publications

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“…Furthermore, Twist1 has been shown to elevate the expression of cancer testis antigens (CTAs) such as NY‐ESO1 and MAGEA4 in ESCC 56,57 . As CTAs such as preferentially expressed antigen of melanoma and REC8 have been associated with cancer stem‐like cells in melanoma 58 and colorectal cancer, 59 as well as poorly differentiated cSCC, 60,61 it is possible that Twist1 regulates stemness and cSCC development at least in part through its effects on CTAs.…”

Section: Twist1mentioning

confidence: 99%

Twist1 as a target for prevention of cutaneous squamous cell carcinoma

Wang

Rho

Eguiarte-Solomon³

et al. 2022

Molecular Carcinogenesis

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Cutaneous squamous cell carcinoma (cSCC) represents an important clinical problem requiring novel approaches for both prevention and treatment. The transcription factor, Twist-related protein 1 (Twist1), has been identified as having a key mechanistic role in the development and progression of cSCC. Studies in relevant mouse models of cSCC have shown that Twist1 regulates epithelial-mesenchymal transition (EMT) and stemness driving progression and metastasis of cSCC. In addition, further research has shown that Twist1 regulates the balance between keratinocyte proliferation and differentiation and therefore impacts earlier stages of cSCC development. Through use of keratinocyte specific Twist1 knockout models, a role for this gene in keratinocyte stem cell homeostasis has been revealed. As a transcription factor, Twist1 regulates a large number of genes both in a positive, as well as a negative manner across several interdependent pathways. Studies in keratinocyte specific knockout models have shown that Twist1 upregulates the expression of genes involved in proliferation, stemness, and EMT while downregulating the expression of genes associated with differentiation. Furthermore, a number of compounds, including naturally occurring compounds, have been identified that target Twist1 and can block its effects in cancer cells and in keratinocytes in vivo. Collectively, the current understanding of Twist1 function in cSCC development and progression suggests that it represents a potential target for prevention and treatment of cSCC.

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Section: Twist1mentioning

confidence: 99%

Twist1 as a target for prevention of cutaneous squamous cell carcinoma

Wang

Rho

Eguiarte-Solomon³

et al. 2022

Molecular Carcinogenesis

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Downregulation of short‐stature homeobox protein 2 suppresses gastric cancer cell growth and stemness in vitro and in vivo via inactivating wnt/β‐catenin signaling

Chen,

Li,

Sun

2024

Drug Development Research

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Gastric cancer (GC) a prevalent form of cancer globally. Previous research suggests that SHOX2 may have a role in promoting cancer progression. However, the role of SHOX2 in GC is not well understood. Based on data from TCGA_GC data set, SHXO2 levels were examined in normal and GC tissues. Patients in the TCGA_GC cohort were divided into high‐ and low‐SHOX2 level groups for analysis of overall survival (OS), functional enrichment, and immune infiltration. Furthermore, experiments were conducted to investigate the impact of SHOX2 on GC cell function through gain‐ and loss‐of‐function experiments. Utilizing data from public databases, SHOX2 mRNA levels were found to be elevated in GC tissues compared to normal control, this finding was confirmed by RT‐qPCR, western blot analysis, and immune‐histochemical analyses. Elevated SHOX2 levels could serve as an independent indicator of poor prognosis in GC patients. Furthermore, SHOX2 levels had a negative correlation with CD8 T cells and CD4 memory activated T cells, and a positive correlation with of M0 macrophages in GC patients. Functional analyses revealed that SHOX2 deficiency notably suppressed GC cell proliferation, migration, and invasion. Additionally, SHOX2 deficiency was shown to suppress stemness in GC cells in vitro and in vivo via inactivating wnt/β‐catenin signaling. Collectively, SHOX2 may serve as a prognostic marker for GC patients, and downregulation of SHOX2 could effectively impede GC cell growth and stemness by inactivating the wnt/β‐catenin signaling pathway. These findings underscore the potential of SHOX2 as a promising therapeutic target for GC.

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Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell‐Like Properties in Osteosarcoma

Tsai,

Lien,

Wang

et al. 2024

Environmental Toxicology

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Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B‐cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis‐HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin‐resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin‐resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment.

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REC8 enhances stemness and promotes metastasis of colorectal cancer through BTK/Akt/β-catenin signaling pathway

Cited by 8 publications

References 31 publications

Twist1 as a target for prevention of cutaneous squamous cell carcinoma

Twist1 as a target for prevention of cutaneous squamous cell carcinoma

Downregulation of short‐stature homeobox protein 2 suppresses gastric cancer cell growth and stemness in vitro and in vivo via inactivating wnt/β‐catenin signaling

Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell‐Like Properties in Osteosarcoma

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