Alterations in Calcium Signaling Pathways in Breast Cancer

Abstract

Breast cancer is the second most common cancer in women and the fifth cause contributing to death due to the cancer condition. It is essential to deeply understand the complex cellular mechanisms leading to this disease. There are multiple connections between calcium homeostasis alterations and breast cancer in the literature, but no consensus links the mechanism to the disease prognosis. Among the cells contributing to the breast cancer are the breast telocytes, which connect through gap junctions to other cells, including cancer cells and myoepithelial cells. Multiple proteins (i.e., voltage-gated calcium channels, transient receptor potential channels, STIM and Orai proteins, ether à go-go potassium channels, calcium-activated potassium channels, calcium-activated chloride channels, muscarinic acetylcholine receptors, etc.) coupled with calcium signaling pathways undergo functional and/or expression changes associated with breast cancer development and progression, and might represent promising pharmacological targets. Unraveling the mechanisms of altered calcium homeostasis in various breast cells due to the cancer condition might contribute to personalized therapeutic approaches.

Divergence of mutational signatures in association with breast cancer subtype

“…40 Numerous studies described the involvement of calcium signaling and transport in tumorigenesis 41 and specifically in BC. 42 It is not clear how deregulation of calcium homeostasis might induce mutations; however, growing evidence suggest that calcium bears modulating effects upon the DNA repair activities of proteins such as RAD51, 43 AMPK, 44 EXO1, 45 and Ku80. 46 Moreover, Notch receptors are calcium-dependent 47 and Notch1 itself was detected as a regulator of DNA damage response in leukemia 48 ; in BC, Notch signaling pathway is known to be aberrantly activated, 49 and finally Notch1 was reported to actuate ER-dependent transcription in ER+ BC cells.…”

“…A plethora of evidence supports the role of estrogen as a regulator of calcium absorption and reabsorption 40 . Numerous studies described the involvement of calcium signaling and transport in tumorigenesis 41 and specifically in BC 42 . It is not clear how deregulation of calcium homeostasis might induce mutations; however, growing evidence suggest that calcium bears modulating effects upon the DNA repair activities of proteins such as RAD51, 43 AMPK, 44 EXO1, 45 and Ku80 46 .…”

Ca2+ Signaling as the Untact Mode during Signaling in Metastatic Breast Cancer

“…Recent studies have demonstrated that Ca 2+ plays a crucial role not only in malignant proliferation but also in cancer metastasis [ 55 , 56 , 57 , 58 , 59 , 60 ]. Breast cancer is considered a metastatic cancer due to its aggressive features [ 61 ].…”