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iScience

iScience

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Stiff extracellular matrix activates the transcription factor ATF5 to promote proliferation of cancer cells

Published:17 February 2025 DOI: 10.1016/j.isci.2025.112057 PMID: 40124511
Seiichiro Ishihara,?Atsushi Enomoto,?Akihiro Sakai,?Tadashi Iida,?Shoichiro Tange,?Noriyuki Kioka,?Akihiro Nukuda,?Ayaka Ichikawa Nagasato,?Motoaki Yasuda,?Takashi Tokino,?Hisashi Haga

Abstract

Cancer tissues are stiffer than normal tissues. Carcinogenesis stiffens the extracellular matrix (ECM) of cancerous tissues, to which cancer cells respond by activating transcription factors, such as YAP/TAZ, Twist1, and β-catenin, which further elevate their malignancy. However, these transcription factors are also expressed in normal tissues. Therefore, inhibiting these factors in order to treat cancer may lead to severe side effects. Here, we show that activating transcription factor 5 (ATF5), highly expressed in tumors, is activated by ECM stiffness and promotes the proliferation of cancer cells, including that of pancreatic cancer cells and lung cancer cells. In addition, ATF5 suppressed the expression of early growth response 1 (EGR1), thereby accelerating cancer cell proliferation. Stiff ECMs trigger the JAK-MYC pathway which activates ATF5. JAK activation was actomyosin independent whereas MYC induction was actomyosin dependent. These results demonstrate the critical role played by ATF5 in the mechanotransduction process seen in cancers.

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Procduct Name CAS Molecular Formula Supplier Price
MYCi361 2289690-31-7 C26H16ClF9N2O2 57 suppliers Inquiry
MYCi361 2289690-31-7 C26H16ClF9N2O2 57 suppliers Inquiry
MYCi361 2289690-31-7 C26H16ClF9N2O2 57 suppliers Inquiry
MYCi361 2289690-31-7 C26H16ClF9N2O2 57 suppliers Inquiry
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