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

Abstract

Metastatic features of breast cancer in the brain are considered a common pathology in female patients with late-stage breast cancer. Ca2+ signaling and the overexpression pattern of Ca2+ channels have been regarded as oncogenic markers of breast cancer. In other words, breast tumor development can be mediated by inhibiting Ca2+ channels. Although the therapeutic potential of inhibiting Ca2+ channels against breast cancer has been demonstrated, the relationship between breast cancer metastasis and Ca2+ channels is not yet understood. Thus, we focused on the metastatic features of breast cancer and summarized the basic mechanisms of Ca2+-related proteins and channels during the stages of metastatic breast cancer by evaluating Ca2+ signaling. In particular, we highlighted the metastasis of breast tumors to the brain. Thus, modulating Ca2+ channels with Ca2+ channel inhibitors and combined applications will advance treatment strategies for breast cancer metastasis to the brain.

A non-canonical role for pyruvate kinase M2 as a functional modulator of Ca2+ signalling through IP3 receptors

“…Rather, the activity of IP 3 Rs represents the summative effects of various modifiers including accessory proteins, and factors such as ions, nucleotides, and redox status[1].The different modes of regulation of IP 3 R by accessory proteins provides the means to alterCa 2+ signals depending on cell type and physiological status. Significantly, there is a growing number of examples where the modulation of IP 3 R-mediated Ca 2+ signals by accessory proteins is hijacked by cancer cells to provide a survival or metastatic advantage[13,[45][46][47][48][49][50][51].The present work suggests that PKM2 may similarly provide an advantageous modulation of IP 3 R-mediated Ca 2+ signals in cancer. PKM2 is highly expressed in cancer cells, where in most cases its expression correlates with poor prognosis[52].…”

Identification of MAGEC2/CT10 as a High Calcium-Inducible Gene in Triple-Negative Breast Cancer

“…In the tumor microenvironment and especially at metastatic sites, Ca 2+ is a predominant but one of the least studied factors in TNBC biology. Although it is well established that circulating Ca 2+ is associated with cancer progression ( 9 , 10 ), the effects of high Ca 2+ on tumor growth varies from one cancer type to another ( 54 , 63 , 64 ). For instance, high extracellular Ca 2+ inhibits the proliferation of colon cancer and parathyroid cells ( 54 , 65 ) but stimulates both the proliferation and metastatic potentials of breast and prostate cancer cells ( 55 ).…”

Identifying Lymph Node Metastasis-related Factors in Breast Cancer using Differential Modular and Mutational Structural Analysis

“…Several studies have reported that calcium signaling pathways are essential to cancer progression. In particular, calcium signaling pathways regulate key processes, from inflammation to apoptosis, that are involved in breast cancer tumorigenesis, [52] metastasis, [53] and resistance to chemotherapy.…”