The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Abstract

Cancer and stromal cells, which include (cancer‐associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation. Further, the stroma vasculature impacts the metabolism of the cells by providing or limiting the availability of oxygen and nutrients. Autophagy, a lysosomal catabolic process with homeostatic and prosurvival functions, influences the behavior of cancer cells, affecting a variety of processes such as the survival in metabolic harsh conditions, the invasive growth, the development of immune and chemo resistance, the maintenance of stem‐like properties, and dormancy. Further, autophagy is involved in the secretion and the signaling of promigratory cytokines. Cancer‐associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro‐inflammatory cytokines and the release of autophagy‐derived metabolites and substrates. Interrupting the metabolic cross‐talk between cancer cells and cancer‐associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer.

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

“…UBE2L6 depletion can activate autophagy and regulate the chemosensitivity of esophageal cancer cells [33]. Serving as either oncogenic or anti-tumor regulator, autophagy is widely implicated in regulation of stem maintenance, proliferation, invasion, metastasis, and therapy resistance of OC [27,28,35]. Here, we validated that UBE2T inhibition could promote autophagy, subsequently suppress the malignant characteristics of OC cells via constraining AKT/mTOR.…”

“…The roles of autophagy in OC have been widely explored [27,28]. Considering the regulatory effects of UBE2T on AKT [18] and p53 [12], which are vital regulators of autophagy [28], we explored the function of UBE2T in autophagy of OC cells.…”

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer

“…In OC, CXCL14 secreted by CAFs stimulates LINC0009 to promote OC growth and invasion ( Curtis et al, 2019 ; Jiang et al, 2020 ). Moreover, CAFs may affect autophagy in OC cells through a series of pro-inflammatory cytokines, autophagy-derived substrates, and metabolites, leading to OC progression ( Thuwajit et al, 2018 ; Jiang et al, 2020 ). In high-grade serous OC, high levels of infiltration of CD8+ T cells are usually associated with favorable outcomes ( Goode et al, 2017 ).…”

The chemokine lymphotactin and its recombinant variants in oral cancer cell regulation

“…Cancer progression is a dynamic process involving changes in cancer cells and the TME through secretion of pro-tumour factors by CAF. In ovarian cancer, CAF have been shown to secrete numerous chemokines such as CCL5, CXCL1, CXCL 11, CXCL12, cytokines and soluble factors facilitating its progression (Thuwajit et al, 2017).…”