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

Asghar, Muhammad; Törnquist, Kid

doi:10.3390/ijms21051739

Cited by 27 publications

(32 citation statements)

References 123 publications

(155 reference statements)

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“…While the initiation of migration is faster in WT HEK-293 cells, our observations show that the overall migration level of ORAI1 KO cells, with significantly reduced SOCE, is equivalent to WT HEK-293 cells. Our data do not eliminate the involvement of other Ca 2+ signaling pathways such as receptor-operated Ca 2+ entry and the activation of TRPCs, which have been shown to be involved the migration process [ 58 , 59 , 60 , 61 ]. We believe that compensatory mechanisms might have occurred to maintain the physiological migration properties of HEK-293 cells.…”

Section: Discussioncontrasting

confidence: 73%

Impact of SOCE Abolition by ORAI1 Knockout on the Proliferation, Adhesion, and Migration of HEK-293 Cells

Bokhobza¹,

Ziental-Gelus²,

Allart³

et al. 2021

Cells

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Store-operated calcium entry (SOCE) provided through channels formed by ORAI proteins is a major regulator of several cellular processes. In immune cells, it controls fundamental processes such as proliferation, cell adhesion, and migration, while in cancer, SOCE and ORAI1 gene expression are dysregulated and lead to abnormal migration and/or cell proliferation. In the present study, we used the CRISPR/Cas9 technique to delete the ORAI1 gene and to identify its role in proliferative and migrative properties of the model cell line HEK-293. We showed that ORAI1 deletion greatly reduced SOCE. Thereby, we found that this decrease and the absence of ORAI1 protein did not affect HEK-293 proliferation. In addition, we determined that ORAI1 suppression did not affect adhesive properties but had a limited impact on HEK-293 migration. Overall, we showed that ORAI1 and SOCE are largely dispensable for cellular proliferation, migration, and cellular adhesion of HEK-293 cells. Thus, despite its importance in providing Ca2+ entry in non-excitable cells, our results indicate that the lack of SOCE does not deeply impact HEK-293 cells. This finding suggests the existence of compensatory mechanism enabling the maintenance of their physiological function.

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Section: Discussioncontrasting

confidence: 73%

Impact of SOCE Abolition by ORAI1 Knockout on the Proliferation, Adhesion, and Migration of HEK-293 Cells

Bokhobza¹,

Ziental-Gelus²,

Allart³

et al. 2021

Cells

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“…The literature supports the fact that both subtypes (TRPC and TRPV) are capable of forming complexes with STIM1 and Orai1 to create sustained calcium entry [ 16 , 17 ]. The overexpression of a variety of members from the TRP family has been correlated with increased EMT [ 18 ] and poor patient prognosis [ 19 , 20 ].…”

Section: Calcium Channelsmentioning

confidence: 99%

Role of Calcium Homeostasis in Modulating EMT in Cancer

Jones

Hazlehurst

2021

Biomedicines

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Calcium is essential for cells to perform numerous physiological processes. In cancer, the augmentation of calcium signaling supports the more proliferative and migratory cells, which is a characteristic of the epithelial-to-mesenchymal transition (EMT). By genetically and epigenetically modifying genes, channels, and entire signaling pathways, cancer cells have adapted to survive with an extreme imbalance of calcium that allows them to grow and metastasize in an abnormal manner. This cellular remodeling also allows for the evasion of immune surveillance and the development of drug resistance, which lead to poor prognosis in patients. Understanding the role calcium flux plays in driving the phenotypes associated with invasion, immune suppression, metastasis, and drug resistance remains critical for determining treatments to optimize clinical outcomes and future drug discovery.

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“…There is increasing evidence that different ion channels play an important role in various human cancers 12 , modulating the migration, invasion and proliferation of cancer cells 13,14 . Ca 2+ in ux plays a critical role in the function and fate of many different cell types, and TRPC3 is known to regulate Ca 2+ ux by a nonselective permeation pathway 15 .…”

Section: Introductionmentioning

confidence: 99%

“…TRPC3 present in the plasma membrane and mitochondrial inner membrane 16,17 . As a regulator, TRPC3 was reported to promote the migration and invasion of several different tumor cell types 12 . For example, TRPC3 channels promote human ovarian cancer cells growth 12,18 , and it can modulate the growth and apoptosis resistance of triple negative breast cancer cells via the TRPC3/RASA4/MAPK signaling pathway 19 .…”

Section: Introductionmentioning

confidence: 99%

“…As a regulator, TRPC3 was reported to promote the migration and invasion of several different tumor cell types 12 . For example, TRPC3 channels promote human ovarian cancer cells growth 12,18 , and it can modulate the growth and apoptosis resistance of triple negative breast cancer cells via the TRPC3/RASA4/MAPK signaling pathway 19 . Moreover, LncRNA SNHG5 plays a critical role in the growth and invasion process of melanoma via the miR-26a-5p/TRPC3 signaling pathway 20 .…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stem Cells Derived from Adipose Accelerate the Progression of Colon Cancer by Inducing a MT-CAFs Phenotype via TRPC3/NF-KB Axis

Xue

Gao

et al. 2021

Preprint

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Background: There is increasing evidence that mesenchymal stem cells (MSCs) help shape the tumor microenvironment and promote tumor progression, and ion channels might play a critical role in this process. Methods: Gene chip was used for a general analysis of gene expression changes in MSC-transformed CAF cells (MT-CAFs). We screened out the ion channel protein TRPC3 with WB detecion and lentivirus knockdown. Calcium influx was detected by two-photon microscope. MTS and Transwell detected growth, migration, and invasion of MT-CAFs and HCT116 cells. Bioinformatic tools and clinical specimens were to assess the relationship between TRPC3 and surrvival.Results: We screened out the ion channel protein TRPC3 with significantly increased expression, which caused calcium influx, and further activated the NF-KB signaling pathway. Knockdown or inhibition of TRPC3 in MSCs significantly reduced the activation of NF-KB, and decreased the growth, migration, and invasion of MT-CAFs. After TRPC3 knockdown, the ability of MT- CAFs to promote tumor migration and invasion was impaired. Conversely, the upregulation of TRPC3 expression in MT-CAFs had the opposite effect. In vivo, TRPC3 expressed on MSCs also contributed to the tumorigenesis and progression of cancer cells. In addition, the Oncomine and GEPIA databases showed that TRPC3 expression is higher in colon cancer tissue compared with normal colon tissues, and is positively correlated with the expression of the CAF genes alpha-smooth muscle (α-SMA/ACTA2) and fibroblast activation protein Alpha (FAP). The disease-free survival of patients with positive TRPC3 expression in mesenchymal cells was significantly shorter than in those with negative expression. Conclusions: These results indicate that TRPC3 expressed on MT-CAFs plays a critical role in tumor progression via the NF-KB signaling pathway, and is correlated with poor prognosis in colon cancer patients. Therefore, TRPC3 may be a novel therapeutic target for the treatment of colon cancer.

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

Cited by 27 publications

References 123 publications

Impact of SOCE Abolition by ORAI1 Knockout on the Proliferation, Adhesion, and Migration of HEK-293 Cells

Impact of SOCE Abolition by ORAI1 Knockout on the Proliferation, Adhesion, and Migration of HEK-293 Cells

Role of Calcium Homeostasis in Modulating EMT in Cancer

Mesenchymal Stem Cells Derived from Adipose Accelerate the Progression of Colon Cancer by Inducing a MT-CAFs Phenotype via TRPC3/NF-KB Axis

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