Ca2+ Signaling and Its Potential Targeting in Pancreatic Ductal Carcinoma

Abstract

Pancreatic cancer (PC) is a major cause of cancer-associated mortality in Western countries (and estimated to be the second cause of cancer deaths by 2030). The main form of PC is pancreatic adenocarcinoma, which is the fourth most common cause of cancer-related death, and this situation has remained virtually unchanged for several decades. Pancreatic ductal adenocarcinoma (PDAC) is inherently linked to the unique physiology and microenvironment of the exocrine pancreas, such as pH, mechanical stress, and hypoxia. Of them, calcium (Ca2+) signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer. Mutations or aberrant expression of key proteins that control Ca2+ levels can cause deregulation of Ca2+-dependent effectors that control signaling pathways determining the cells’ behavior in a way that promotes pathophysiological cancer hallmarks, such as enhanced proliferation, survival and invasion. So far, it is essentially unknown how the cancer-associated Ca2+ signaling is regulated within the characteristic landscape of PDAC. This work provides a complete overview of the Ca2+ signaling and its main players in PDAC. Special consideration is given to the Ca2+ signaling as a potential target in PDAC treatment and its role in drug resistance.

A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer

“…For example, gaba suppresses PAAD by inhibiting the β-adrenergic cascade and nicotine-induced cell proliferation ( Al-Wadei et al, 2011 ; Al-Wadei et al, 2013 ; Al-Wadei et al, 2016 ). cAMP has both pro- and anti-tumor effects in malignancies ( Tagliaferri et al, 1988 ; Ligumsky et al, 2012 ; Almahariq et al, 2015 ); To our surprise, the calcium signaling pathway and the neuroactive ligand-receptor interaction pathway, both of which are associated with a poor prognosis ( Bettaieb et al, 2021 ; Qian et al, 2021 ), were downregulated in the high-risk group. However, the link between pyroptosis and these pathways is currently unknown and needs further investigation.…”

TRPV6 Calcium Channel Targeting by Antibodies Raised against Extracellular Epitopes Induces Prostate Cancer Cell Apoptosis

“…As for rb79 and rb82, their binding to TRPV6 led to the transient activation of the latter while activating calcium currents and increasing capacitive calcium entry—deleterious for a cancer cell by inducing its death [ 30 , 31 , 32 ]. In our SOCE experiments using siRNA, we could not completely ablate the effects of TRPV6 activation, since the efficiency of siRNA is not absolute [ 16 , 19 ] and enough protein still remains to partially sustain the observed effects.…”

Precision oncology: Artificial intelligence, circulating cell‐free DNA, and the minimally invasive detection of pancreatic cancer—A pilot study

“…Another important pathway is the Rap1 signaling pathway, which plays a crucial role in regulating key events related to tumor cell migration, invasion, and metastasis 50 . Moreover, the calcium signaling pathway was found to be significant, with calcium playing a central role in the migration, invasion, and metastasis of PC cells 51 . The PI3K‐Akt signaling pathway was also identified, and its frequent activation is well‐established in promoting PC aggressiveness 52 .…”

“…50 Moreover, the calcium signaling pathway was found to be significant, with calcium playing a central role in the migration, invasion, and metastasis of PC cells. 51 The PI3K-Akt signaling pathway was also identified, and its frequent activation is well-established in promoting PC aggressiveness. 52 Among the pathways directly related to cancer, "pathways in cancer" and "pancreatic cancer" signaling showed the possible involvement of several differentially methylated genes in our study.…”