American Association for Cancer Research
15417786mcr200186-sup-238189_2_supp_6535587_qnb1b8.pdf (80.21 kB)

Supplementary Figure 4 from Autocrine Leukemia Inhibitory Factor Promotes Esophageal Squamous Cell Carcinoma Progression via Src Family Kinase-Dependent Yes-Associated Protein Activation

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journal contribution
posted on 2023-04-03, 17:41 authored by Tetsuro Kawazoe, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Yoshihiko Maehara, Masaki Mori, Koji Taniguchi

The effects of LIF knockdown by shRNAs on the expression of EMT-related transcriptional factors in human ESCC




Uehara Memorial Foundation

Kanae Foundation for the Promotion of Medical Science

Astellas Foundation for Research on Metabolic Disorders

SENSHIN Medical Research Foundation

Bristol-Myers Squibb

MSD Life Science Foundation

Toray Science Foundation



The IL6 family of cytokines, including IL6 and leukemia-inhibitory factor (LIF), are induced during inflammation and are also expressed in many types of cancer where they play an important role in tumor development. IL6 family cytokines mainly activate the JAK–STAT3 pathway via the coreceptor, gp130, and IL6 is known to activate the Src family kinase (SFK)–Yes-associated protein (YAP) pathway. The current study investigated the role of autocrine LIF in human esophageal squamous cell carcinoma (ESCC) that highly expresses LIF. LIF knockdown had various effects on cancer cells, including profound changes in gene expression, suppression of cell proliferation, migration/invasion and sphere formation, and induction of apoptosis. Similar to IL6, LIF activated the SFK–YAP pathway as well as the JAK–STAT3 pathway. LIF-induced YAP activation was more important for cancer cell proliferation than LIF-induced STAT3 activation, and concomitant YAP and STAT3 activation completely compensated for the role of LIF in human ESCC growth. We also confirmed that SFK activation and LIF expression were correlated with YAP activation in human ESCC clinical samples. Furthermore, simultaneous inhibition of the SFK–YAP and JAK–STAT3 pathways in human ESCC cells was more effective at suppressing cell proliferation than single inhibition, and autocrine LIF signaling promoted human ESCC growth in vivo. Therefore, the LIF–SFK–YAP axis may represent a new therapeutic target for human ESCC. Autocrine LIF signaling promotes human ESCC progression via SFK-dependent YAP activation and is a new potential target of treatment for human ESCC.

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