Transient Receptor Potential Canonical 1 (TRPC1) Channels as Regulators of Sphingolipid and VEGF Receptor Expression

Asghar, Muhammad; Magnusson, Melissa; Kemppainen, Kati; Sukumaran, Pramod; Löf, Christoffer; Pulli, Ilari; Kalhori, Veronica; Törnquist, Kid

doi:10.1074/jbc.m115.643668

Cited by 49 publications

(49 citation statements)

References 50 publications

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“…We have shown that TRPC1 is a potent regulator of both migration and invasion in follicular thyroid cancer ML-1 cells [91]. The mechanisms involved appear to depend on the at least MAPK/ERK1/2, MMP2 and-9, and HIF1α.…”

Section: Trpc Channels Migration and Invasionmentioning

confidence: 88%

Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

Asghar

Törnquist

2020

IJMS

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Calcium (Ca2+) is perhaps the most versatile signaling molecule in cells. Ca2+ regulates a large number of key events in cells, ranging from gene transcription, motility, and contraction, to energy production and channel gating. To accomplish all these different functions, a multitude of channels, pumps, and transporters are necessary. A group of channels participating in these processes is the transient receptor potential (TRP) family of cation channels. These channels are divided into 29 subfamilies, and are differentially expressed in man, rodents, worms, and flies. One of these subfamilies is the transient receptor potential canonical (TRPC) family of channels. This ion channel family comprises of seven isoforms, labeled TRPC1–7. In man, six functional forms are expressed (TRPC1, TRPC3–7), whereas TRPC2 is a pseudogene; thus, not functionally expressed. In this review, we will describe the importance of the TRPC channels and their interacting molecular partners in the etiology of cancer, particularly in regard to regulating migration and invasion.

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Section: Trpc Channels Migration and Invasionmentioning

confidence: 88%

Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

Asghar

Törnquist

2020

IJMS

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“…Transient receptor potential C1, which belongs to the TRP canonical channel subfamily, is activated by direct suction of the membrane . It is necessary for directional migration, such as chemotaxis, but is not necessary for basal migration . During cell migration, TRPC1 localizes to the leading edges of cells, which is proposed to contribute to the local elevations in intracellular Ca 2+ at the very front of cells .…”

Section: Dysregulation Of Ion Transport In Metastatic Cancer Cellsmentioning

confidence: 99%

“…Thus, TRPC1 plays an important role in polarization during cell migration by aiding protrusion of the leading edge rather than by aiding rear retraction. Although few reports have implicated TRPC1 in cancer metastasis, some reports have indicated that TRPC1 is necessary for cell migration of invasive tumors, such as thyroid cancer and glioma …”

Section: Dysregulation Of Ion Transport In Metastatic Cancer Cellsmentioning

confidence: 99%

Cell volume regulation in cancer cell migration driven by osmotic water flow

2019

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Cancer metastasis is the most frequent cause of death for patients with cancer. The main current treatment for cancer metastasis is chemotherapy targeting cancer cells’ ability to proliferate. However, some types of cancer cells show resistance to chemotherapy. Recently, cancer cell migration has become the subject of interest as a novel target of cancer therapy. Cell migration requires many factors, such as the cytoskeleton, cell‐matrix adhesion and cell volume regulation. Here, we focus on cell volume regulation and the role of ion/water transport systems in cell migration. Transport proteins, such as ion channels, ion carriers, and aquaporins, are indispensable for cell volume regulation under steady‐state conditions and during exposure to osmotic stress. Studies from the last ~25 years have revealed that cell volume regulation also plays an important role in the process of cell migration. Water flow in accordance with localized osmotic gradients generated by ion transport contributes to the driving force for cell migration. Moreover, it has been reported that metastatic cancer cells have higher expression of these transport proteins than nonmetastatic cancer cells. Thus, ion/water transport proteins involved in cell volume regulation and cell migration could be novel therapeutic targets for cancer metastasis. In this review, after presenting the importance of ion/water transport systems in cell volume regulation, we discuss the roles of transport proteins in a pathophysiological context, especially in the context of cancer cell migration.

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“…A previous study showed that TRPC1 inhibits migration through decreasing the sphingosine1-phosphate 3 receptor and vascular endothelial growth factor receptor 2 levels in thyroid cancer cells [13]. In NSCLCs, TRPC6 inhibition suppresses the expression of fibronectin and the tight junction protein zonula occluden protein-1 (ZO-1), leading to a decrease in migration ability [11].…”

Section: Discussionmentioning

confidence: 99%

Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells

Chang

Cheng

Tsai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glioblastoma, also known as glioblastoma multiforme (GBM), is a fast-growing type of tumor that is the most aggressive brain malignancy in adults. According to GEO profile analysis, patients with high transient receptor potential canonical 3 (TRPC3) expression have poor survival rates. The aim of this study is to evaluate the effects of Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), a selective TRPC3 channel blocker, on the proliferation and migration of human glioblastoma cells. Methods: We first analyzed the TRPC3 mRNA expression in Gene Expression Omnibus (GEO) database. Then, TRPC3 protein expression was analyzed by Western blotting in three human GBM cell lines. The survival rate was measured by sulforhodamine B. JC1 staining was used to analyze the mitochondria membrane potential by flow cytometric analysis. Besides, the migration and invasion were evaluated by wound healing and Transwell assays. Annexin V and 7-aminoactinomycin D staining was used to monitor the apoptosis by flow cytometric analysis. The expression of apoptotic-related and migration-related proteins after Pyr3 treatment was detected by Western blotting. In addition, an orthotropic xenograft mouse model was used to assay the effect of Pyr3 in the in vivo study. Results: Basis on the results of bioinformatics study, glioma patients with higher TRPC3 expression had a shorter survival time than those with lower TRPC3 expression. GBM cell proliferation was decreased by Pyr3 treatment. The migration and invasion abilities of glioma cells were also inhibited via focal adhesion kinase and myosin light chain dephosphorization after Pyr3 treatment. Moreover, Pyr3 induced caspase-dependent apoptosis and mitochondria membrane potential imbalance in the GBM cells. In a xenograft animal model, Pyr3 in combination with temozolomide (TMZ) inhibited GBM tumor growth. Conclusion: Pyr3 inhibited GBM tumor growth in vitro and in vivo. Pyr3-TMZ combination therapy could be used to treat glioblastoma in the future.

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Transient Receptor Potential Canonical 1 (TRPC1) Channels as Regulators of Sphingolipid and VEGF Receptor Expression

Cited by 49 publications

References 50 publications

Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

Cell volume regulation in cancer cell migration driven by osmotic water flow

Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells

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