Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Che, Nan; Yang, Zheng; Liu, Xingzhe; Li, Mengxuan; Feng, Ying; Zhang, Chengye; Li, Chao; Cui, Yan; Xuan, Yanhua

doi:10.1111/jcmm.16169

Cited by 18 publications

(9 citation statements)

References 42 publications

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“…AMPK inhibition would lead to deregulation of the normal progression of the cell cycle. Accordingly, LETM1-KD reduced the expression of cancer stemness-related genes, increased AMPK activation, arrested cell cycle, lowered the number and size of tumor spheroids, and markedly inhibited cell proliferation (Che et al, 2020;Li et al, 2020;Piao et al, 2020).…”

Section: Letm1 In Cancermentioning

confidence: 97%

LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling

et al. 2021

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Nearly 2 decades since its discovery as one of the genes responsible for the Wolf-Hirschhorn Syndrome (WHS), the primary function of the leucine-zipper EF-hand containing transmembrane 1 (LETM1) protein in the inner mitochondrial membrane (IMM) or the mechanism by which it regulates mitochondrial Ca2+ handling is unresolved. Meanwhile, LETM1 has been associated with the regulation of fundamental cellular processes, such as development, cellular respiration and metabolism, and apoptosis. This mini-review summarizes the diversity of cellular functions impacted by LETM1 and highlights the multiple roles of LETM1 in health and disease.

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Section: Letm1 In Cancermentioning

confidence: 97%

LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling

et al. 2021

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“…It is worth mentioning that the down-regulation of LETM1 induced autophagy in colorectal cancer (CRC) cells, and the autophagy inhibitor 3-methyladenine reversed the inhibitory effects of LETM1 silencing on proliferation and stemness. A further analysis indicated that the suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS, activated the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and, thus, initiated autolysis [ 38 ]. In our current study, the LETM1 protein was significantly suppressed, and the AMPK pathway was promoted in the AP (autolysis) group, compared to the AXP (non-autolysis) group, indicating that the suppression of LETM1 induced the AMPK pathway and initiated autolysis in P. pastoris .…”

Section: Resultsmentioning

confidence: 99%

The Transcriptomic Mechanism of a Novel Autolysis Induced by a Recombinant Antibacterial Peptide from Chicken Expressed in Pichia pastoris

Wang

Sheng

et al. 2022

Molecules

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Autolysis is a common physiological process in eukaryotic cells that is often prevented or applied, especially in yeast expression systems. In this study, an antimicrobial peptide from chicken (AMP) was recombinantly expressed in the Pichia pastoris expression system, which induced a series of cellular autolysis phenotypes after methanol treatment, such as the aggregated, lysed, irregular, and enlarged cell morphology, while the cells expressing a recombinant aflatoxin-detoxifizyme (ADTZ) were not autolyzed. A comparative transcriptomic analysis showed that the transcriptomic profiles of cells derived from the autolysis and non-autolysis groups were well discriminated, suggesting that the mechanisms of autolysis were at the transcriptional level. A further differential expression gene (DEG) analysis showed that the DEGs from the two groups were involved mainly in autophagy, the MAPK signaling pathway, transcriptional factors, the central carbon metabolism, anti-stress functions, and so on. In the autolysis group, the cell activity was significantly reduced with the MAPK signaling pathway, the central carbon metabolism was down-regulated, and components of the cytoplasm-to-vacuole targeting (CVT) and mitophagy pathways were up-regulated, suggesting that the autophagy involved in the trafficking of intracellular molecules in the vacuole and mitochondrion contributed to autolysis, which was regulated by transcriptional factors and signal pathways at the transcriptional level. This study provides a theoretical basis for genetic modifications to prevent or utilize cell autolysis in the recombinant protein expression system.

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“…Some of these proteins, including OCT4, MYC, KLF4, and SOX2 (Yamanaka factors), are universal, considering that they are typical of both cancer and normal stem cells and are considered essential for stem-related phenotypes [ 107 ]. The regulation of other markers, though, for instance, NANOG, BMI-1, SNAIL, ALDHs, LGR5, CXCR4, REX-1, Musashi-1, LETM1, and C-met, is considered to be dependent on both the cancer type and the specific phenotype of the CSCs that we want to analyze (e.g., drug-resistant, tumorigenic, metastatic) [ 35 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. Studying the expression of specific genes both at the transcriptional and translation level, as well as the activity and localization of these proteins, is useful in assessing the enrichment of CSC properties [ 118 , 119 , 120 , 121 , 122 , 123 ].…”

Section: Cancer Stem Cells (Cscs)mentioning

confidence: 99%

The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression

Tsochantaridis

Roupas

Mohlin

et al. 2023

Life

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Cancer is a multifactorial, complex disease exhibiting extraordinary phenotypic plasticity and diversity. One of the greatest challenges in cancer treatment is intratumoral heterogeneity, which obstructs the efficient eradication of the tumor. Tumor heterogeneity is often associated with the presence of cancer stem cells (CSCs), a cancer cell sub-population possessing a panel of stem-like properties, such as a self-renewal ability and multipotency potential. CSCs are associated with enhanced chemoresistance due to the enhanced efflux of chemotherapeutic agents and the existence of powerful antioxidant and DNA damage repair mechanisms. The distinctive characteristics of CSCs make them ideal targets for clinical therapeutic approaches, and the identification of efficient and specific CSCs biomarkers is of utmost importance. Aldehyde dehydrogenases (ALDHs) comprise a wide superfamily of metabolic enzymes that, over the last years, have gained increasing attention due to their association with stem-related features in a wide panel of hematopoietic malignancies and solid cancers. Aldehyde dehydrogenase 1B1 (ALDH1B1) is an isoform that has been characterized as a marker of colon cancer progression, while various studies suggest its importance in additional malignancies. Here, we review the basic concepts related to CSCs and discuss the potential role of ALDH1B1 in cancer development and its contribution to the CSC phenotype.

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Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Cited by 18 publications

References 42 publications

LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling

LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling

The Transcriptomic Mechanism of a Novel Autolysis Induced by a Recombinant Antibacterial Peptide from Chicken Expressed in Pichia pastoris

The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression

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