Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR–Hippo–YAP pathway

Bian, Sainan; Yang, Yun; Liang, Wenquan; Zhang, Kecheng; Chen, Lin; Zhang, Zhong-Tao

doi:10.1111/nyas.14466

Cited by 34 publications

(26 citation statements)

References 49 publications

(63 reference statements)

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“…Zhang et al suggested that LIFR promoted prostate cancer tumorigenesis and metastasis 34 . Bian et al reported that LIF/LIFR promoted the malignant biological behavior of gastric cancer cells by Hippo/Yes‐associated protein signaling 35 . However, whether LIFR is responsible for circ_0011780/miR‐626 axis in lung cancer progression is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0001073 targets miR‐626/LIFR axis to inhibit lung cancer progression

Li¹,

Cao²,

Wan

et al. 2021

Environmental Toxicology

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Circular RNAs (circRNAs) are associated with lung cancer progression. However, it is unclear whether and how circRNA hsa_circ_0001073 (circ_0001073) are involved in lung cancer progression. circ_0001073, microRNA (miR)-626, and leukemia inhibitory factor receptor (LIFR) abundances were determined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, invasion, and apoptosis were analyzed by cell counting kit-8, transwell analysis and flow cytometry, respectively. The target correlation was tested by dual-luciferase reporter analysis or RNA immunoprecipitation. Results showed that circ_0001073 abundance was downregulated in lung cancer cells. circ_0001073 constrained cell viability and invasion and facilitated apoptosis in lung cancer cells. miR-626 was targeted via circ_0001073, and circ_0001073 inhibited lung cancer progression via reducing miR-626 expression. LIFR was targeted via miR-626, and miR-626 knockdown constrained cell viability and invasion and facilitated apoptosis in lung cancer cells via up-regulating LIFR. circ_0001073 increased LIFR expression via miR-626 in lung cancer cells. In conclusion, circ_0001073 represses lung cancer progression via miR-626/LIFR axis, indicating the potential value of circ_0001073 in lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Hsa_circ_0001073 targets miR‐626/LIFR axis to inhibit lung cancer progression

Li¹,

Cao²,

Wan

et al. 2021

Environmental Toxicology

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“…Other studies have also associated LIF signalling with EMP features such as increased cell migration, invasion, CSC properties and metastasis, reporting both promoting and inhibitory roles, despite not always showing a direct link between LIF and EMP. In gastric cancer, LIF promoted proliferation, colony formation, invasion, migration and tumour growth by inhibiting the Hippo pathway, resulting in increased YAP nuclear translocation and transcriptional activity, giving rise to cancer cells with decreased E-cadherin and increased MMP7 protein levels [ 104 ]. Interestingly, LIF promoted mesenchymal epithelial transition in lung cancer cells through the LIF/LIFR/p-ERK/pS727-STAT3 signalling pathway leading to increased metastasis [ 42 ].…”

Section: Role Of Lif On Epithelial-mesenchymal Plasticitymentioning

confidence: 99%

The Role of the IL-6 Cytokine Family in Epithelial–Mesenchymal Plasticity in Cancer Progression

Abaurrea

Araujo

Caffarel

2021

IJMS

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Epithelial–mesenchymal plasticity (EMP) plays critical roles during embryonic development, wound repair, fibrosis, inflammation and cancer. During cancer progression, EMP results in heterogeneous and dynamic populations of cells with mixed epithelial and mesenchymal characteristics, which are required for local invasion and metastatic dissemination. Cancer development is associated with an inflammatory microenvironment characterized by the accumulation of multiple immune cells and pro-inflammatory mediators, such as cytokines and chemokines. Cytokines from the interleukin 6 (IL-6) family play fundamental roles in mediating tumour-promoting inflammation within the tumour microenvironment, and have been associated with chronic inflammation, autoimmunity, infectious diseases and cancer, where some members often act as diagnostic or prognostic biomarkers. All IL-6 family members signal through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway and are able to activate a wide array of signalling pathways and transcription factors. In general, IL-6 cytokines activate EMP processes, fostering the acquisition of mesenchymal features in cancer cells. However, this effect may be highly context dependent. This review will summarise all the relevant literature related to all members of the IL-6 family and EMP, although it is mainly focused on IL-6 and oncostatin M (OSM), the family members that have been more extensively studied.

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“…Although the precise reasons may differ among cancers, few have made significant forays into the underlying molecular mechanisms by which LIFRβ plays a role as a metastasis and tumorigenic suppressor. The most relevant underlying molecular mechanisms demonstrated have defined connections to the tumor suppressor Hippo pathway, and links between LIFRβ and the Hippo pathway have been demonstrated in breast ( 59 ), clear renal cell carcinoma ( 64 ), and gastric cancer ( 93 ). Although LIF-LIFR signaling activates a variety of pathways associated with cancer progression such as JAK/STAT and MAPK, more potent and significant activators of these pathways already exist and are potential targets for treatment.…”

Section: Lif and Lifrβ Expression In Cancermentioning

confidence: 99%

“…Additionally, a study of gastric cancer found that higher levels of LIF and LIFR were associated with increased proliferation, invasion, and metastasis ( 93 ). Interestingly they determined that LIF-LIFR signaling actually inhibited Scribble localization to cell membranes, thereby preventing the inactivation of YAP through the Hippo pathway.…”

Section: Lifr Activation Of Yes: Yap Activity Downstream Of Lifmentioning

confidence: 99%

“…Interestingly they determined that LIF-LIFR signaling actually inhibited Scribble localization to cell membranes, thereby preventing the inactivation of YAP through the Hippo pathway. When YAP was inhibited via shRNA, the effect of LIF-LIFR signaling on cancer growth and migration was lost ( 93 ). In a dose dependent manner, LIF decreased the phosphorylation of MST and LATS, implying that LIF-LIFR signaling is somehow inhibiting the Hippo pathway and allowing YAP to remain active, rather than directly activating YES to activate YAP ( 93 ).…”

Section: Lifr Activation Of Yes: Yap Activity Downstream Of Lifmentioning

confidence: 99%

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Emerging Perspectives on Leukemia Inhibitory Factor and its Receptor in Cancer

2021

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Tumorigenesis and metastasis have deep connections to inflammation and inflammatory cytokines, but the mechanisms underlying these relationships are poorly understood. Leukemia Inhibitory Factor (LIF) and its receptor (LIFR), part of the interleukin-6 (IL-6) cytokine family, make up one such ill-defined piece of the puzzle connecting inflammation to cancer. Although other members of the IL-6 family have been shown to be involved in the metastasis of multiple types of cancer, the role of LIF and LIFR has been challenging to determine. Described by others in the past as enigmatic and paradoxical, LIF and LIFR are expressed in a diverse array of cells in the body, and the narrative surrounding them in cancer-related processes has been vague, and at times even contradictory. Despite this, recent insights into their functional roles in cancer have highlighted interesting patterns that may allude to a broader understanding of LIF and LIFR within tumor growth and metastasis. This review will discuss in depth the signaling pathways activated by LIF and LIFR specifically in the context of cancer–the purpose being to summarize recent literature concerning the downstream effects of LIF/LIFR signaling in a variety of cancer-related circumstances in an effort to begin teasing out the intricate web of contradictions that have made this pair so challenging to define.

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Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR–Hippo–YAP pathway

Cited by 34 publications

References 49 publications

Hsa_circ_0001073 targets miR‐626/LIFR axis to inhibit lung cancer progression

Hsa_circ_0001073 targets miR‐626/LIFR axis to inhibit lung cancer progression

The Role of the IL-6 Cytokine Family in Epithelial–Mesenchymal Plasticity in Cancer Progression

Emerging Perspectives on Leukemia Inhibitory Factor and its Receptor in Cancer

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