Emerging Role of Mucolipins TRPML Channels in Cancer

Santoni, Giorgio; Santoni, Matteo; Maggi, Federica; Marinelli, Oliviero; Morelli, Maria Beatrice

doi:10.3389/fonc.2020.00659

Cited by 20 publications

(17 citation statements)

References 62 publications

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“…Increased expression of TPCs has been implicated in cancer cell migration and dissemination in bladder, liver and hematological tumors, while genetic and pharmacologic inhibition of TPCs has been linked to diminished adhesion and migration of invasive tumor cells and formation of lung metastases in a breast cancer mouse model (Nguyen et al, 2017;Faris et al, 2018;Alharbi and Parrington, 2019). Similarly, increased TRPML1 expression in head and neck squamous cell and bladder urothelial carcinoma inversely correlated with patient prognosis, and has been associated with chemotherapy resistance in endometrial adenocarcinoma cells (Faris et al, 2018;Jung et al, 2019;Santoni et al, 2020).…”

Section: Chemoresistance and Cancer Evasion Through Lysosomal Pathwaysmentioning

confidence: 99%

Lysosomes and Cancer Progression: A Malignant Liaison

Machado

Annunziata

Vlekkert

et al. 2021

Front. Cell Dev. Biol.

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During primary tumorigenesis isolated cancer cells may undergo genetic or epigenetic changes that render them responsive to additional intrinsic or extrinsic cues, so that they enter a transitional state and eventually acquire an aggressive, metastatic phenotype. Among these changes is the alteration of the cell metabolic/catabolic machinery that creates the most permissive conditions for invasion, dissemination, and survival. The lysosomal system has emerged as a crucial player in this malignant transformation, making this system a potential therapeutic target in cancer. By virtue of their ubiquitous distribution in mammalian cells, their multifaced activities that control catabolic and anabolic processes, and their interplay with other organelles and the plasma membrane (PM), lysosomes function as platforms for inter- and intracellular communication. This is due to their capacity to adapt and sense nutrient availability, to spatially segregate specific functions depending on their position, to fuse with other compartments and with the PM, and to engage in membrane contact sites (MCS) with other organelles. Here we review the latest advances in our understanding of the role of the lysosomal system in cancer progression. We focus on how changes in lysosomal nutrient sensing, as well as lysosomal positioning, exocytosis, and fusion perturb the communication between tumor cells themselves and between tumor cells and their microenvironment. Finally, we describe the potential impact of MCS between lysosomes and other organelles in propelling cancer growth and spread.

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Section: Chemoresistance and Cancer Evasion Through Lysosomal Pathwaysmentioning

confidence: 99%

Lysosomes and Cancer Progression: A Malignant Liaison

Machado

Annunziata

Vlekkert

et al. 2021

Front. Cell Dev. Biol.

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“…Pharmacological or genetic knock-down of TRPML1 induces oxidative stress and free radical generations in retinal pigmented epithelial cells (24). Even though the role of TRPML1 as ROS sensor has been demonstrated (53,54), the consequences of TRPML1 downregulation in glioma cells are still unknown. In agreement with Coblentz et al data, likely due to ROS levels below the resolution level of DCFDA, the fluorescent ROS sensitive dye used in the cytofluorimetric analysis, we were unable to detect the ROS production in siTRPML1 T98 and U251 cells at any time after transfection (27).…”

Section: Discussionmentioning

confidence: 99%

Knock-Down of Mucolipin 1 Channel Promotes Tumor Progression and Invasion in Human Glioblastoma Cell Lines

et al. 2021

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Among cancers that affect the central nervous system, glioblastoma is the most common. Given the negative prognostic significance of transient receptor potential mucolipin 1 (TRPML1) channel reduction in patients with glioblastoma, as discussed in previous publications, the aim of the current study was to investigate the biological advantage of TRPML1 loss for glioma cells. Human glioblastoma primary cancer cells (FSL and FCL) and glioblastoma cell lines (T98 and U251) were used for that purpose. TRPML1 silencing in T98 cells induces defective autophagy, nitric oxide (NO) production, and cathepsin B-dependent apoptosis in the first 48 h and then apoptotic-resistant cells proliferate with a high growth rate with respect to control cells. In U251 cells, knock-down of TRPML1 stimulates NO generation and protein oxidation, arrests cell cycle at G2/M phase, and induces autophagy leading to cathepsin B-dependent senescence. Finally, in both cell lines, the long-term effects of TRPML1 silencing promote survival and invasion capacity with respect to control cells. Silencing of TRPML1 also affects the phenotype of glioblastoma primary cells. FSL cells show increased proliferation ability, while FCL cells enter into senescence associated with an increased invasion ability. In conclusion, although the molecular heterogeneity among different glioblastoma cell lines mirrors the intercellular heterogeneity in cancer cells, our data support TRPML1 downregulation as a negative prognostic factor in glioblastoma.

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“…It is believed that impaired lysosomal Ca 2+ signaling is a culprit in malignant tumor development [ 122 ]. Indeed, emerging evidence has demonstrated that lysosomal Ca 2+ signaling underlies several cancer hallmarks involving proliferation, metastasis, and angiogenesis and contributes to multidrug resistance in cancer therapy [ 122 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 ]. Here we discuss the roles of the two major Ca 2+ permeable channels, TRPMLs and TPCs, in cancer.…”

Section: Lysosomal Ca 2+ Autophagy and Cancementioning

confidence: 99%

Lysosomal Calcium Channels in Autophagy and Cancer

Huang

Dong

2021

Cancers

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Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca2+ stores and their roles in autophagy and human cancer progression.

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Emerging Role of Mucolipins TRPML Channels in Cancer

Cited by 20 publications

References 62 publications

Lysosomes and Cancer Progression: A Malignant Liaison

Lysosomes and Cancer Progression: A Malignant Liaison

Knock-Down of Mucolipin 1 Channel Promotes Tumor Progression and Invasion in Human Glioblastoma Cell Lines

Lysosomal Calcium Channels in Autophagy and Cancer

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