Estrogen enhances the proliferation and migration of ovarian cancer cells by activating transient receptor potential channel C3

Recent studies have suggested that FSH plays an important role in ovarian epithelial carcinogenesis. We demonstrated that FSH stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis and facilitates neovascularisation. Our previous work has shown that transient receptor potential channel C3 (TRPC3) contributes to the progression of human ovarian cancer. In this study, we further investigated the interaction between FSH and TRPC3. We found that FSH stimulation enhanced the expression of TRPC3 at both the mRNA and protein levels. siRNA-mediated silencing of TRPC3 expression inhibited the ability of FSH to stimulate proliferation and blocked apoptosis in ovarian cancer cell lines. FSH stimulation was associated with the up-regulation of TRPC3, while also facilitating the influx of Ca2+ after treatment with a TRPC-specific agonist. Knockdown of TRPC3 abrogated FSH-stimulated Akt/PKB phosphorylation, leading to decreased expression of downstream effectors including survivin, HIF1-α and VEGF. Ovarian cancer specimens were analysed for TRPC3 expression; higher TRPC3 expression levels correlated with early relapse and worse prognosis. Association with poor disease-free survival and overall survival remained after adjusting for clinical stage and grade. In conclusion, TRPC3 plays a significant role in the stimulating activity of FSH and could be a potential therapeutic target for the treatment of ovarian cancer, particularly in postmenopausal women with elevated FSH levels.

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Transient Receptor Potential Melastatin 8 (TRPM8) Channel Regulates Proliferation and Migration of Breast Cancer Cells by Activating the AMPK-ULK1 Pathway to Enhance Basal Autophagy

Frontiers in Oncology ◽

10.3389/fonc.2020.573127 ◽

2020 ◽

Vol 10 ◽

Author(s):

Yuan Huang ◽

Shi Li ◽

Zhenhua Jia ◽

Weiwei Zhao ◽

Cefan Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Melastatin ◽

Ampk Activity ◽

Transient Receptor ◽

And Migration ◽

Proliferation And Migration

The calcium-permeable cation channel TRPM8 (transient receptor potential melastatin 8) is a member of the TRP superfamily of cation channels that is upregulated in various types of cancer with high levels of autophagy, including prostate, pancreatic, breast, lung, and colon cancers. Autophagy is closely regulated by AMP-activated protein kinase (AMPK) and plays an important role in tumor growth by generating nutrients through degradation of intracellular structures. Additionally, AMPK activity is regulated by intracellular Ca2+ concentration. Considering that TRPM8 is a non-selective Ca2+-permeable cation channel and plays a key role in calcium homoeostasis, we hypothesized that TRPM8 may control AMPK activity thus modulating cellular autophagy to regulate the proliferation and migration of breast cancer cells. In this study, overexpression of TRPM8 enhanced the level of basal autophagy, whereas TRPM8 knockdown reduced the level of basal autophagy in several types of mammalian cancer cells. Moreover, the activity of the TRPM8 channel modulated the level of basal autophagy. The mechanism of regulation of autophagy by TRPM8 involves autophagy-associated signaling pathways for activation of AMPK and ULK1 and phagophore formation. Impaired AMPK abolished TRPM8-dependent regulation of autophagy. TRPM8 interacts with AMPK in a protein complex, and cytoplasmic C-terminus of TRPM8 mediates the TRPM8–AMPK interaction. Finally, basal autophagy mediates the regulatory effects of TRPM8 on the proliferation and migration of breast cancer cells. Thus, this study identifies TRPM8 as a novel regulator of basal autophagy in cancer cells acting by interacting with AMPK, which in turn activates AMPK to activate ULK1 in a coordinated cascade of TRPM8-mediated breast cancer progression.

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Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor

AJP Cell Physiology ◽

10.1152/ajpcell.00614.2008 ◽

2009 ◽

Vol 297 (2) ◽

pp. C360-C368 ◽

Cited By ~ 85

Author(s):

Elie Abed ◽

Robert Moreau

Keyword(s):

Growth Factor ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Platelet Derived Growth Factor ◽

Human Osteoblast ◽

Osteoblast Proliferation ◽

Transient Receptor ◽

And Migration ◽

Stimulation Of ◽

Proliferation And Migration

Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg2+) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg2+ and melastatin-like transient receptor potential 7 (TRPM7), known as Mg2+ channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg2+, enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg2+ concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg2+ influx, proliferation, and migration. Our results indicate that extracellular Mg2+ and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg2+ deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis.

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Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src

PLoS ONE ◽

10.1371/journal.pone.0189524 ◽

2018 ◽

Vol 13 (1) ◽

pp. e0189524 ◽

Cited By ~ 7

Author(s):

Mian M. K. Shahzad ◽

Mildred Felder ◽

Kai Ludwig ◽

Hannah R. Van Galder ◽

Matthew L. Anderson ◽

...

Keyword(s):

Ovarian Cancer ◽

Linoleic Acid ◽

Er Stress ◽

Cancer Cells ◽

Conjugated Linoleic Acid ◽

Ovarian Cancer Cells ◽

And Migration ◽

Proliferation And Migration

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Sepiapterin inhibits cell proliferation and migration of ovarian cancer cells via down-regulation of p70S6K-dependent VEGFR-2 expression

Oncology Reports ◽

10.3892/or.2011.1335 ◽

2011 ◽

Cited By ~ 1

Author(s):

Shin Choi

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Down Regulation ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

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Transient receptor potential cation 3 channel regulates melanoma proliferation and migration

The Journal of Physiological Sciences ◽

10.1007/s12576-016-0480-1 ◽

2016 ◽

Vol 67 (4) ◽

pp. 497-505 ◽

Cited By ~ 13

Author(s):

Kayoko Oda ◽

Masanari Umemura ◽

Rina Nakakaji ◽

Ryo Tanaka ◽

Itaru Sato ◽

...

Keyword(s):

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor ◽

And Migration ◽

Proliferation And Migration

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Transient receptor potential channel C3 contributes to the progression of human ovarian cancer

Oncogene ◽

10.1038/onc.2008.475 ◽

2009 ◽

Vol 28 (10) ◽

pp. 1320-1328 ◽

Cited By ~ 81

Author(s):

S L Yang ◽

Q Cao ◽

K C Zhou ◽

Y J Feng ◽

Y Z Wang

Keyword(s):

Ovarian Cancer ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Channel ◽

Human Ovarian Cancer ◽

Transient Receptor

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Expression of Mitochondrial Progesterone Receptor (PR-M) in Ovarian Cancer and Its Effect on Cell Metastasis Induced by Progesterone

10.21203/rs.3.rs-285751/v1 ◽

2021 ◽

Author(s):

Qingqing Yang ◽

Chang Duan ◽

Haofan Wang ◽

Dongyuan Jiang ◽

Yaping Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Progesterone Receptor ◽

Cancer Cells ◽

Cell Lines ◽

Ovarian Tumors ◽

Ovarian Cancer Cells ◽

Borderline Tumor ◽

And Migration ◽

Cancer Tissues ◽

Proliferation And Migration

Abstract Background: PR-M refers to a novel truncated progesterone receptor located on the outer membrane of mitochondria, capable of facilitating the proliferation of leiomyoma cells and breast cancer cells, as well as inhibiting apoptosis as impacted by progesterone or progesterone agonists. However, its role in ovarian tumors has not yet been elucidated.Objective: To study the expression of PR-M in different ovarian tumor tissues and normal tissues, and the effect exerted by progesterone on the proliferation and migration of SKOV-3 cells that achieve high PR-M expression.Methods: Real- time PCR and Western blot were employed for determining PR-M levels in cell lines, non-cancer tissues and ovarian cancer tissues. By immunohistochemistry, PR-M protein expression in benign tumor, borderline tumor and epithelial carcinoma was detected, and the clinicopathological characteristics between PR-M and cancer were analyzed. Furthermore, CCK-8 and scratch test were performed to explore the proliferation and migration of SKOV-3 cells exhibiting high PR-M expression.Results: PR-M increased significantly in cancer tissues and ovarian cancer cell lines, in comparison to normal cells and non-cancer tissues. The abnormal expression showed a significant correlation with intraperitoneal metastasis, lymph node metastasis, clinically related stage and CA125 level, suggesting that high PR-M expression may affect the progression of ovarian tumors. During the cell experiment, PR-M achieved the maximum expression in SKOV-3 cells (PR-A / B(-)). As impacted by progesterone, SKOV-3 cells (PR-A / B(-)) achieved the enhanced proliferation and migration. Besides, the enhancing effect was dose and time-dependent.Conclusion: PR-M is critical to develop ovarian cancer. Progesterone may facilitate the proliferation and migration of ovarian cancer cells exhibiting high PR-M expression.

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