Role of cancer‑associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non‑small cell lung cancer (Review)

Chen, Congcong; Hou, Jie; Yu, Sizhe; Li, Wenyuan; Wang, Xiao; Sun, Huizhen; Qin, Tao; Claret, François X.; Guo, Hui; Liu, Zhiyan

doi:10.3892/ol.2021.12674

Cited by 24 publications

(18 citation statements)

References 66 publications

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“…Our understanding of the role of the tumor microenvironment (TME) over the recurrence and relapse of cancer has been growing in the last years. The physical properties and composition of the TME generate signals to alter cancer cell proliferation and migration [1,2] and it is thought that the TME could represent a protective niche for tumoral cells during antitumoral therapies [3,4]. The extracellular matrix (ECM) is one of the most relevant elements that compose the TME [5] and it represents a scaffold structure for cells.…”

Section: Introductionmentioning

confidence: 99%

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

Peláez

Ochoa

Pariente

et al. 2021

Cancers

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Sterculic acid (SA) is a cyclopropenoid fatty acid isolated from Sterculia foetida seeds. This molecule is a well-known inhibitor of SCD1 enzyme, also known as ∆9-desaturase, which main function is related to lipid metabolism. However, recent studies have demonstrated that it also modifies many other pathways and the underlying gene expression. SCD overexpression, or up-regulated activity, has been associated with tumor aggressiveness and poor prognosis in many cancer types. Scd1 down-regulation, with different inhibitors or molecular strategies, reduces tumor cell survival and cell proliferation, as well as the chemoresistance associated with cancer stem cell presence. However, SA effects over cancer cell migration and extracellular matrix or adhesion molecules have not been described in cancer cells up to now. We used different migration assays and qPCR gene expression analysis to evaluate the effects of SA treatment in cancer cells. The results reveal that SA induces tumoral cell death at high doses, but we also observed that lower SA-treatments induce cell adhesion-migration capacity reduction as a result of modifications in the expression of genes related to integrins and extracellular matrix compounds. Overall, the functional and transcriptomic findings suggest that SA could represent a new inhibitor activity of epithelial to mesenchymal transition.

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Section: Introductionmentioning

confidence: 99%

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

Peláez

Ochoa

Pariente

et al. 2021

Cancers

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“…Lung adenocarcinoma is one of the most CAF-rich cancers. The role of CAFs in resistance to chemotherapy of lung adenocarcinoma is well appreciated [167,168]. Cisplatin treatment increases Interleukin-11 (IL-11) levels in CAFs which protects lung adenocarcinoma cells from apoptosis [169].…”

Section: Interleukins Secreted By Cafsmentioning

confidence: 99%

Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

Neophytou

Trougakos

Erin

et al. 2021

Cancers

168

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The ability of tumor cells to evade apoptosis is established as one of the hallmarks of cancer. The deregulation of apoptotic pathways conveys a survival advantage enabling cancer cells to develop multi-drug resistance (MDR), a complex tumor phenotype referring to concurrent resistance toward agents with different function and/or structure. Proteins implicated in the intrinsic pathway of apoptosis, including the Bcl-2 superfamily and Inhibitors of Apoptosis (IAP) family members, as well as their regulator, tumor suppressor p53, have been implicated in the development of MDR in many cancer types. The PI3K/AKT pathway is pivotal in promoting survival and proliferation and is often overactive in MDR tumors. In addition, the tumor microenvironment, particularly factors secreted by cancer-associated fibroblasts, can inhibit apoptosis in cancer cells and reduce the effectiveness of different anti-cancer drugs. In this review, we describe the main alterations that occur in apoptosis-and related pathways to promote MDR. We also summarize the main therapeutic approaches against resistant tumors, including agents targeting Bcl-2 family members, small molecule inhibitors against IAPs or AKT and agents of natural origin that may be used as monotherapy or in combination with conventional therapeutics. Finally, we highlight the potential of therapeutic exploitation of epigenetic modifications to reverse the MDR phenotype.

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“…Indeed, it has been found that Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) that belong to the Hippo pathway are activated in lung fibrosis. To this purpose, Xu et al through single-cell RNA sequencing found that the YAP/TAZ, TGF-β, Wnt, and the PI3K axis were activated in the AECs of IPF patients [152,153]. They suggested that mTOR/PI3K/AKT signalling contributed to IPF pathogenesis, both increasing the proliferation of lung epithelial cells and lung fibroblasts.…”

Section: The Onset and Progression Of Ipf: The Leading Role Of Tgf-β1mentioning

confidence: 99%

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development

Samarelli

Masciale

Aramini

et al. 2021

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2–4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine–kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

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Role of cancer‑associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non‑small cell lung cancer (Review)

Cited by 24 publications

References 66 publications

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development

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