Review
Cell Biology
Morgan Brisset, Patrick Mehlen, Olivier Meurette, Frederic Hollande
Summary: The heterogeneity of cancer cells plays a significant role in therapeutic failure and post-treatment recurrence. Targeting specific subpopulations responsible for chemoresistance and recurrence may improve treatment outcomes in cancer patients. However, the complexity and incomplete understanding of tumor cell subpopulations make it challenging to achieve this.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jae Hun Shin, Jaekwang Jeong, Jungmin Choi, Jaechul Lim, Ravi K. Dinesh, Jonathan Braverman, Jun Young Hong, Stephen E. Maher, Maria C. Amezcua Vesely, WonJu Kim, Ja-Hyun Koo, Wenwen Tang, Dianqing Wu, Holly N. Blackburn, Rosa M. Xicola, Xavier Llor, Omer Yilmaz, Je-Min Choi, Alfred L. M. Bothwell
Summary: Enhanced stemness in colorectal cancer is closely associated with the Wnt ligand DKK2, which plays a critical role in promoting tumor progression by increasing LGR5-expressing cells. DKK2 activates the proto-oncogene tyrosine-protein kinase Src through degrading HNF4 alpha 1 protein, contributing to the aggressiveness of colorectal cancer.
Article
Cell Biology
Guangyu Ji, Wenjuan Zhou, Jingyi Du, Juan Zhou, Dong Wu, Man Zhao, Liping Yang, Aijun Hao
Summary: The study identified PCGF1 as a crucial epigenetic regulator in sustaining the stem cell-like phenotype of CRC, with increased PCGF1 expression correlated with cancer progression and poor prognosis. Knockdown of PCGF1 inhibited CRC stem cell proliferation and enrichment, ultimately impairing tumor growth in vivo. Mechanistically, PCGF1 activates transcription of CRC stem cell markers by altering histone trimethylation marks on their promoters.
CELL DEATH & DISEASE
(2021)
Editorial Material
Biochemistry & Molecular Biology
Christopher G. Hubert, Shaun R. Stauffer, Justin D. Lathia
Summary: A new signaling network that connects epigenetic regulation to self-renewal and therapeutic resistance in cancer stem cells is revealed in this study.
Review
Gastroenterology & Hepatology
Ka-Hei Lam, Stephanie Ma
Summary: Cancer stem cells (CSCs) are a major cause of treatment failure and tumor recurrence in hepatocellular carcinoma (HCC). In addition to intrinsic regulators, extrinsic regulators in the tumor microenvironment also play a crucial role in the regulation of CSCs.
Article
Biochemistry & Molecular Biology
Dan-Yun Ruan, Ting Li, Ying-Nan Wang, Qi Meng, Yang Li, Kai Yu, Min Wang, Jin-Fei Lin, Li-Zhi Luo, De-Shen Wang, Jun-Zhong Lin, Long Bai, Ze-Xian Liu, Qi Zhao, Xiang-Yuan Wu, Huai-Qiang Ju, Rui-Hua Xu
Summary: FTO protein levels are decreased in CRC tissues, and this reduction is correlated with a high recurrence rate and poor prognosis. Hypoxia inhibits FTO protein expression mainly through an increase in ubiquitin-mediated protein degradation.
Article
Biochemistry & Molecular Biology
Aleksandra Salagacka-Kubiak, Dawid Zawada, Lias Saed, Radzislaw Kordek, Agnieszka Jelen, Ewa Balcerczak
Summary: ABCG2 is a cell membrane pump encoded by the ABCG2 gene, which can protect cells against compounds initiating and/or intensifying neoplasia and is considered a marker of cancer stem cells. Its prognostic significance in colorectal cancer remains unclear. Using publicly available data, ABCG2 was shown to be underexpressed in colon and rectum adenocarcinomas, and this downregulation could result from the methylation level of some sites of the ABCG2 gene. However, no association was found between ABCG2 expression level and survival of colorectal cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Kun Liu, Yan-Chi Li, Yu Chen, Xiao-Bao Shi, Zi-Hao Xing, Zheng-Jie He, Sheng-Te Wang, Wei-Jing Liu, Peng-Wei Zhang, Ze-Zhong Yu, Xue-Mei Mo, Mei-Wan Chen, Zhe-Sheng Chen, Zhi Shi
Summary: Colorectal cancer is a common malignancy with high mortality largely due to chemotherapy resistance. This study demonstrated that the ATM kinase inhibitor AZ32 could sensitize ABCG2-overexpressing colorectal cancer cells to specific chemotherapeutic drugs by retaining them inside cells. Molecular docking analysis predicted that AZ32 stably located in the transmembrane domain of ABCG2, providing a potential strategy to reverse multidrug resistance in colorectal cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Zhao-liang Yu, Yu-feng Chen, Bin Zheng, Ze-rong Cai, Yi-feng Zou, Jia Ke, Ping Lan, Feng Gao, Xiao-jian
Summary: The study reveals the critical role of TMEM17 in colorectal cancer, showing that TMEM17 depletion can suppress the proliferation of CRC cells and increase sensitivity to chemotherapy drugs. Enrichment analysis indicates that TMEM17 expression is associated with the activation of the Wnt/beta-catenin pathway, and clinical samples show higher TMEM17 expression in tumors is associated with poor survival in CRC patients.
CANCER CELL INTERNATIONAL
(2021)
Article
Medicine, Research & Experimental
Yihong Guan, Metis Hasipek, Dongxu Jiang, Anand D. Tiwari, Dale R. Grabowski, Simona Pagliuca, Sunisa Kongkiatkamon, Bhumika Patel, Salendra Singh, Yvonne Parker, Thomas LaFramboise, Daniel Lindner, Mikkael A. Sekeres, Omar Y. Mian, Yogen Saunthararajah, Jaroslaw P. Maciejewski, Babal K. Jha
Summary: Eltrombopag binds to the TET2 catalytic domain and inhibits its dioxygenase activity, leading to the expansion of normal hematopoietic stem cells and the prevention of neoplastic evolution in TET2 mutant malignant myeloid cells. This finding provides a scientific rationale for the treatment of myeloid malignancies associated with TET2 mutations or TET deficiency.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Jing Li Huang, Masanori Oshi, Itaru Endo, Kazuaki Takabe
Summary: Clinically, patients with high CD24 expression in colorectal cancer tumors have better disease-specific and overall survival rates, and tumors with high CD133, CD24, and CD44 expression are associated with increased EGFR, KRAS, and Ki67 expression. Moreover, CD133-high/CD24-low tumors show potential for predicting worse prognosis in colorectal cancer patients.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Zhibao Zheng, Na Luan, Kai Tu, Feiyan Liu, Jianwei Wang, Jianguo Sun
Summary: PCDH7 expression in colorectal cancer cells is positively correlated with cell proliferation and drug resistance, while negatively correlated with cell migration and invasion. PCDH7 mediates drug resistance by inhibiting cell apoptosis through upregulating Mcl-1 expression and activating the Wnt signaling pathway. The Mcl-1 inhibitor S63845 can attenuate the anti-apoptotic effect of PCDH7 and sensitizes PCDH7-overexpressing colorectal cancer cells to ABT-263.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Qing Guo, Shuai Shen, Gefei Guan, Chen Zhu, Cunyi Zou, Jingyuan Cao, Wen Cheng, Xiaoyan Xu, Juanhan Yu, Zhiguo Lin, Guoli Wang, Ling Chen, Peng Cheng, Anhua Wu
Summary: Glioblastoma (GBM) shares common signaling pathways involving TIM-3, an immune checkpoint, between tumor and non-tumor cells. The study reveals that TIM-3 in glioma cells not only regulates the malignant behaviors of glioma cells but also induces macrophage migration and transition to an anti-inflammatory/protumorigenic phenotype through the TIM-3/IL6 signal. Blocking this feedback loop may provide a novel therapeutic strategy for GBM.
Article
Medicine, General & Internal
Xiaoyan Zhang, Ling Yang, Wanjun Lei, Qiang Hou, Ming Huang, Rongjing Zhou, Tariq Enver, Shixiu Wu
Summary: This study investigated the tumor heterogeneity and clonal evolution of colorectal cancer-initiating cells (CRCICs) using single-cell whole-exome sequencing (scWES) and bulk cell targeted exome sequencing (TES). The results revealed that CD133(+)CD44(-) cells were the likely origin of colorectal cancer and identified several stemness-related mutant genes. Additionally, predicted neoantigens with potential applications in immunotherapy were identified.
Article
Oncology
Ziwei Liang, Bingrui Wu, Zhi Ji, Weitao Liu, Danfang Shi, Xiaoning Chen, Yuanyan Wei, Jianhai Jiang
Summary: LDN193189 inhibits liver TIC self-renewal, tumorigenicity, and immune escape by targeting CD133 phosphorylation, providing a potential therapeutic approach to targeting the CD133-Galectin-3 axis for liver cancer treatment.