Overview of Ca2+ signaling in lung cancer progression and metastatic lung cancer with bone metastasis

Abstract

Intracellular Ca2+ ions that are thought to be one of the most important second messengers for cellular signaling, have a substantial diversity of roles in regulating a plethora of fundamental cellular physiology such as gene expression, cell division, cell motility and apoptosis. It has been suggestive of the Ca2+ signaling-dependent cellular processes to be tightly regulated by the numerous types of Ca2+ channels, pumps, exchangers and sensing receptors. Consequently, dysregulated Ca2+ homeostasis leads to a series of events connected to elevated malignant phenotypes including uncontrolled proliferation, migration, invasion and metastasis, all of which are frequently observed in advanced stage lung cancer cells. The incidence of bone metastasis in patients with advanced stage lung cancer is estimated in a range of 30% to 40%, bringing about a significant negative impact on both morbidity and survival. This review dissects and summarizes the important roles of Ca2+ signaling transduction in contributing to lung cancer progression, and address the question: if and how Ca2+ signaling might have been engaged in metastatic lung cancer with bone metastasis, thereby potentially providing the multifaceted and promising solutions for therapeutic intervention.

Elucidating Cancer Subtypes by Using the Relationship between DNA Methylation and Gene Expression

“…This pathway is used to identify novel biomarkers and therapeutic targets in lung cancer [61]. Similarly, a calcium signaling pathway, which was over-represented in all the subtypes, contributes to lung cancer progression [62]. We can see that the subtypes are contrasting in terms of the altered pathways.…”

Lung cancer associated with combustion particles and fine particulate matter (PM2.5) - The roles of polycyclic aromatic hydrocarbons (PAHs) and the aryl hydrocarbon receptor (AhR)

“…Dysregulation of Ca 2+ -signaling is frequent in many cancer types and has been linked to tumor progression. Furthermore, aberrant expression of TRP-channel such as TRPC and TRPM has been reported in lung cancer and other cancer types and has been linked to EMT, cell proliferation, invasion and promotion of cell survival and suppression of apoptosis [ 216 , 217 ]. Importantly, these effects have been described for pyrene and phenanthrene, PAHs that traditionally have been considered weak AhR activators due to limited effects on classical AhR:Arnt signaling [ 150 ].…”

Adverse effects of the cancer therapy on osteoclast-mediated bone loss in patients with cancers: a challenge

“…Oestrogen plays an important role in maintaining bone mass in adult women by suppressing bone remodeling and maintaining a balance between osteoblast and osteoclastic activities. Oestrogen alleviates the osteoblastic production of resorptive cytokines, including RANKL, M-CSF and tumor necrosis factor, and at the same time increases the production of antireceptive cytokines (mainly osteoprotegerin) [11]. This leads to increased osteoclastic apoptosis and increased osteoblast activity.…”

“…In bone, OBs and bone marrow stromal cells serve as primary soures of RANKL, M-CSF and osteoprotegerin (OPG). OPG functions as a decoy for RANKL, therefore inhibiting the binding of RANKL to RANK receptor, thereby alleviating osteoclastogenesis [11,12]. Indeed, in vivo studies substantiated that mice deficient for the gene encoding either RANKL or RANK repcetor developed osteopetrosis (a genetically etiological state of elevated bone mass) owing to the impaired OC formation [13].…”