Interaction between IGF2‐PI3K axis and cancer‐associated‐fibroblasts promotes anal squamous carcinogenesis

Cacheux, Wulfran; Lièvre, Astrid; Richon, Sophie; Vacher, Sophie; Alam, Elsy El; Briaux, Adrien; Botty, Rania El; Mariani, Pascale; Bruno, Benedetto; Schnitzler, Anne; Barbazán, Jorge; Roman‐Roman, Sergio; Bièche, Ivan; Dangles‐Marie, Virginie

doi:10.1002/ijc.32178

Cited by 15 publications

(7 citation statements)

References 26 publications

(59 reference statements)

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“… 18 , 19 The regulation of IGF2 in the PI3K/AKT/mTOR signalling pathway indicated that there might be a positive feedback loop between mTOR and IGF2BP3 expression. 20 , 21 However, the molecular mechanisms of IGF2BP3 in NPC are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

Guo

Peng

et al. 2021

J Cellular Molecular Medi

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Nasopharyngeal carcinoma (NPC) has obvious geographical distribution characteristics and is commonly diagnosed in certain regions of east and southeast Asia, such as China. 1 In particular, NPC mainly occurs in the southern provinces of China and ranks first among head and neck malignant tumours in Fujian. Treatment with induction chemotherapy plus concurrent chemoradiotherapy has improved the 5-year overall survival (OS) of patients with stage III-IVB NPC to 86%, while 22% of the patients develop locoregional or distant failures. 2 Therefore, it is necessary to clarify the underlying mechanisms of NPC metastasis and identify novel prognostic factors and targets for NPC.Insulin-like growth factor 2 mRNAs binding protein 3 (IGF2BP3) is a highly conserved member of the insulin-like growth factor 2 mRNAs binding protein family. IGF2BP3 functions as a post-transcriptional

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Section: Introductionmentioning

confidence: 99%

IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

Guo

Peng

et al. 2021

J Cellular Molecular Medi

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“…3 ). The fact that PI3K/AKT signaling pathways regulated CAF-mediated cancer cell proliferation in oral, 136 lung, 137 , 138 gastric, 139 colon, 140 endometrial, 141 and anal 142 cancers. Mechanistically, in gastric cancer, a neutralizing antibody against Nodal attenuated CAF-induced cancer cell proliferation through Nodal-induced activation of the Smad2/3/AKT signal axis.…”

Section: Major Signaling Pathways and Targeted Therapies In Cafsmentioning

confidence: 99%

Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Yang

Liu

et al. 2021

Sig Transduct Target Ther

329

249

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To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling, maintenance of stemness, blood vessel formation, modulation of tumor metabolism, immune response, and promotion of cancer cell proliferation, migration, invasion, and therapeutic resistance. CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers and activators of transcription, epidermal growth factor receptor, Hippo, and nuclear factor kappa-light-chain-enhancer of activated B cells, etc., signaling pathways. These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy. Therefore, a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers. Herein, in this review, we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials. Further, we hypothesize three potential targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential target perturbation, and crosstalk-directed signaling targets, paving the way for CAF-directed or host cell-directed antitumor therapy.

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“…In this study, CAFs from primary tumours were shown to promote stemness characteristics of lung cancer-stem cells (expression of Nanog and Oct3/4), an effect which was shown to be partly dependent on the expression of IGF-II. IGF-II in CAFs is known to accelerate tumour growth in cholangiocarcinoma xenograft models 77 and promotes proliferation of anal squamous cell carcinoma cells 78 . Moreover, expression of IGF-II has been shown to promote differentiation of fibroblasts into myofibroblasts in idiopathic pulmonary fibrosis and scleroderma/systemic sclerosis-associated pulmonary fibrosis 79 .…”

Section: Cellular Procceses In Cafsmentioning

confidence: 99%

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Irvine

Waise

Green

et al. 2021

Sci Rep

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Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with evidence suggesting they represent a heterogeneous population. This study summarises the prognostic role of all proteins characterised in CAFs with immunohistochemistry in non-small cell lung cancer thus far. The functions of these proteins in cellular processes crucial to CAFs are also analysed. Five databases were searched to extract survival outcomes from published studies and statistical techniques, including a novel method, used to capture missing values from the literature. A total of 26 proteins were identified, 21 of which were combined into 7 common cellular processes key to CAFs. Quality assessments for sensitivity analyses were carried out for each study using the REMARK criteria whilst publication bias was assessed using funnel plots. Random effects models consistently identified the expression of podoplanin (Overall Survival (OS)/Disease-specific Survival (DSS), univariate analysis HR 2.25, 95% CIs 1.80–2.82) and α-SMA (OS/DSS, univariate analysis HR 2.11, 95% CIs 1.18–3.77) in CAFs as highly prognostic regardless of outcome measure or analysis method. Moreover, proteins involved in maintaining and generating the CAF phenotype (α-SMA, TGF-β and p-Smad2) proved highly significant after sensitivity analysis (HR 2.74, 95% CIs 1.74–4.33) supporting attempts at targeting this pathway for therapeutic benefit.

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Interaction between IGF2‐PI3K axis and cancer‐associated‐fibroblasts promotes anal squamous carcinogenesis

Cited by 15 publications

References 26 publications

IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

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