scholarly journals The Orai1-AC8 Interplay: How Breast Cancer Cells Escape from Orai1 Channel Inactivation

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1308
Author(s):  
José Sánchez-Collado ◽  
José J. López ◽  
Juan A. Rosado
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cellular Functions ◽  
Cancer Hallmarks ◽  
Channel Inactivation ◽  
Relevant Role ◽  
And Migration ◽  
Adenylyl Cyclase 8 ◽  
Proliferation And Migration

The interplay between the Ca2+-sensitive adenylyl cyclase 8 (AC8) and Orai1 channels plays an important role both in the activation of the cAMP/PKA signaling and the modulation of Orai1-dependent Ca2+ signals. AC8 interacts with a N-terminal region that is exclusive to the Orai1 long variant, Orai1α. The interaction between both proteins allows the Ca2+ that enters the cell through Orai1α to activate the generation of cAMP by AC8. Subsequent PKA activation results in Orai1α inactivation by phosphorylation at serine-34, thus shaping Orai1-mediated cellular functions. In breast cancer cells, AC8 plays a relevant role supporting a variety of cancer hallmarks, including proliferation and migration. Breast cancer cells overexpress AC8, which shifts the AC8-Orai1 stoichiometry in favor of the former and leads to the impairment of PKA-dependent Orai1α inactivation. This mechanism contributes to the enhanced SOCE observed in triple-negative breast cancer cells. This review summarizes the functional interaction between AC8 and Orai1α in normal and breast cancer cells and its relevance for different cancer features.

scholarly journals miR-145 inhibits proliferation and migration of breast cancer cells by directly or indirectly regulating TGF-β1 expression

2017 ◽  
Vol 50 (5) ◽  
pp. 1701-1710 ◽  
Author(s):  
Yanling Ding ◽  
Chunfu Zhang ◽  
Jiahui Zhang ◽  
Nannan Zhang ◽  
Tao Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
And Migration ◽  
Tgf Β1 ◽  
Proliferation And Migration

scholarly journals MARK4 inhibits Hippo signaling to promote proliferation and migration of breast cancer cells

EMBO Reports ◽  
2017 ◽  
Vol 18 (3) ◽  
pp. 420-436 ◽  
Author(s):  
Emad Heidary Arash ◽  
Ahmed Shiban ◽  
Siyuan Song ◽  
Liliana Attisano
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hippo Signaling ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jia Cao ◽  
Xi Wang ◽  
Danni Wang ◽  
Rong Ma ◽  
Xiaohan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Modulation of the uptake of critical nutrients by breast cancer cells by lactate: Impact on cell survival, proliferation and migration

2016 ◽  
Vol 341 (2) ◽  
pp. 111-122 ◽  
Author(s):  
Marta Guedes ◽  
João R. Araújo ◽  
Ana Correia-Branco ◽  
Inês Gregório ◽  
Fátima Martel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
And Migration ◽  
Critical Nutrients ◽  
Proliferation And Migration

scholarly journals 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

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.

scholarly journals Inhibition of the PI3K-AKT-mTOR pathway suppresses the adipocyte-mediated proliferation and migration of breast cancer cells

2020 ◽  
Vol 11 (9) ◽  
pp. 2552-2559 ◽  
Author(s):  
Jae-Yeo Park ◽  
Shi-Eun Kang ◽  
Kwang Seok Ahn ◽  
Jae-Young Um ◽  
Woong Mo Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Pathway ◽  
And Migration ◽  
Proliferation And Migration
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