Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer

We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating isthmus stem cells in the stomach and that IQGAP3 expression is robustly induced in terminally differentiated chief cells and de-differentiated cells following tissue damage. The elevated IQGAP3 expression in c...

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Published iniScience Vol. 25; no. 10; p. 105194
Main Authors Myint, Khine, Chuang, Linda Shyue Huey, Teh, Yu Xuan, Mawan, Nur Astiana, Shi, Edward Jizhong, Mok, Michelle Meng Huang, Nuttonmanit, Napat, Matsuo, Junichi, Li, Ying, Yang, Henry, Okabe, Atsushi, Kaneda, Atsushi, Osato, Motomi, So, Jimmy Bok-Yan, Yong, Wei Peng, Tan, Patrick, Yeoh, Khay Guan, Ito, Yoshiaki
Format Journal Article
LanguageEnglish
Published Elsevier Inc 21.10.2022
Elsevier
Subjects
cancer
Cell biology
stem cells research
Cell biology
cancer
stem cells research
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Summary:We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating isthmus stem cells in the stomach and that IQGAP3 expression is robustly induced in terminally differentiated chief cells and de-differentiated cells following tissue damage. The elevated IQGAP3 expression in cancer and its association with metastasis suggest a fundamental role for IQGAP3 in proliferating cancer stem cells. What causes IQGAP3 upregulation in cancer is unclear. Here, we show that IGF2BP1 and IQGAP3 expression levels are highest in the blastocyst, with both decreasing during adulthood. This suggests that IQGAP3, like IGF2BP1, is an early developmental gene that is aberrantly upregulated upon re-expression of IGF2BP1 during carcinogenesis. IGF2BP1 binds and stabilizes m6A-modified IQGAP3 transcripts. Downstream targets of IGF2BP1, namely SRF and FOXM1, also upregulate IQGAP3 expression. These multiple layers of IQGAP3 regulation, which may safeguard against inappropriate stem cell proliferation, present additional drug targets to inhibit IQGAP3-driven malignant growth. [Display omitted] •Oncofetal protein IGF2BP1 is a key stabilizer of IQGAP3 mRNA•IGF2BP1’s targets SRF and FOXM1 act as additional regulators of IQGAP3 expression•IGF2BP1-SRF-FOXM1-IQGAP3 network contributes to cancer stemness Cell biology; Stem cells research; Cancer
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.105194