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Interactions of Growth Factors, Hormones, and Oncogenes Controlling the Proliferation of Normal and Cancer Cells
Published in Velibor Krsmanović, James F. Whitfield, Malignant Cell Secretion, 2019
James F. Whitfield, Jon P. Durkin
Although the mitogenic first signal is transient, the activated RAS protein associated with the inner surface of the plasma membrane has other long-term effects which mask the initial signal. The protein starts the production and secretion of several autocrine mitogens such as TGFα, TGFβ and PDGF or PDGF-like factors.136,137,223-226,241,242,343-345 These factors keep the cells cycling independently from external factors once their expression has been activated by the mitogenic first signal. The RAS protein also stimulates the production and secretion of the 55-kDa autocrine motility factor (AMF) which mobilizes the cell, and the 92-kDa metalloproteinase which enables the mobilized cell to tunnel through the collagen IV of basement membranes and begin metastasizing.227-229,241,242,346,347
Role of Growth Factors in Neoplastic Processes
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Autocrine factors capable of stimulating DNA synthesis and cell proliferation specifically in the tumor cells of origin in vivo have been isolated from some animal tumors.92 Some autocrine factors may stimulate cell motility and may have a role in the processes of tumor invasion and metastasization. An autocrine motility factor (AMF) was identified in the human melanoma cell line A2058.93 The AMF elicits increases in tumor cell motility and phosphoinositide metabolism via a pertussis toxin-sensitive G protein signal transduction pathway.94 AMF and IGF-I would act in a synergistic manner through independent cell surface receptors to stimulate the motility of tumor cells and may be involved in the process of metastasization.95 The possibility that such factors are involved in the expression of a transformed phenotype is reinforced by the observation that the expression of a cDNA encoding a growth factor in a factor-dependent cell line may result in autonomous growth and tumorigenicity.96 A proposed model for autocrine-regulated proliferation of tumor cell populations would accommodate any growth curve that fits the data.97
Estrogen receptors as potential therapeutic target in endometrial cancer
Published in Journal of Receptors and Signal Transduction, 2023
Payel Guha, Koushik Sen, Piyali Chowdhury, Dilip Mukherjee
GPER takes part in activating several signaling pathways in type-II EC. As reported earlier, E2 binding to GPER can rapidly activate the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) and MAP kinase pathway through nongenomic action, thus resulting in cell proliferation [57,58]. Signaling of majority of these pathways, not all, are mediated via transactivation of EGFR involving nonreceptor tyrosine kinase of Src family [59,60]. GPER also regulate gene expression like C-FOS, CYCLIN A, and D1, CTGF (connective tissue growth factor) and many others [50,52]. A very recent study suggested for the control of microRNA-195 (miRNA-195) on GPER expression in vitro in AN3-CA and HEC-1A cells [61]. In addition, there are many other signaling pathways that interact with GPER to induce a plethora of effects in EC cell lines. IGF-1 triggers cyclin D1 and CTGF expression promoting proliferation and migration of Ishikawa cells [62]. Gankyrin and PTEN shows inverse correlation in EC cell proliferation through GPER/PI3K/Akt pathway activation with E2 [50]. In SPEC-2 cells, proliferation and apoptosis are regulated by autocrine motility factor (AMF) interacting with GPER, following activation of PI3K/Akt pathway. In EC patients, upregulation of both GPER and AMF has been correlated with poor prognosis [63].
Adipokines as therapeutic targets in breast cancer treatment
Published in Expert Opinion on Therapeutic Targets, 2018
Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is a member of the nucleotide pyrophosphatase/phosphodiesterase family of enzymes and is secreted as a catalytically active glycoprotein. ATX was identified as an autocrine motility factor for tumor cells in the early 1990s, and it has found to be identical to lysophospholipase D in the serum [15]. ATX generates lysophosphatidate (LPA), a bioactive phospholipid, from lysophosphatidylcholine (LPC) by hydrolyzing choline from the head group. LPA binds to its receptor and induces various cellular processes via activation of phospholipase C, and the MAPK, PI3K, and (alkaline phosphatase) PhoA pathways [16]. The LPA receptor is a G-protein-coupled receptor, and at least six LPA receptors (LPA1–LPA6) have been identified. LPA1–LPA3 belong to the EDG family (LPA1-EDG2, LPA2-EDG4, LPA3-EDG7), while the structure of LPA4–LPA6 is similar to that of the P2Y nucleotide receptor [17]. ATX-LPA signaling has been reported to be associated with tumor formation, progression, and metastasis [18]. ATX is generated from many cell types including platelets, endothelial cells, fibroblasts, and adipocytes. Among them, ATX secreted by adipocytes specifically affects fat expansion and plasma LPA levels [19].