Nuclear EGFR-PKM2 axis induces cancer stem cell-like characteristics in irradiation-resistant cells

Cancer Letters
Ying ShiYongguang Tao

Abstract

Radiation therapy has become an important tool in the treatment of cancer patients, but most patients relapse within 5 years. Relapse is due to the presence of cancer stem cells (CSCs), but the molecular mechanism of radioresistance in CSCs remains largely elusive. Here, we found that irradiation-resistant (IR) cells exhibited increased stem cell-like properties together with elevated anchorage-independent growth and metastasis ability. EGFR not only leads to increased acquisition of endometrial cancer stem cell markers in radioresistant sublines but is critical for the cancer stem-cell phenotype and tumorigenicity. Moreover, PKM2 functions as an interacting partner of EGFR, which induces the EMT phenotype and stem cell-like properties in IR cells. Finally, we found that the regulatory function of the EGFR-PKM2 axis is dependent on nuclear EGFR. In sum, our study indicated that EGFR and PKM2 directly interact and bind with each other to regulate the transcription of stemness-related genes and promote the stem-like phenotype, thus promoting invasion and metastasis.

Citations

May 23, 2019·Cancer Cell International·Yanzhu LinXinping Cao
Jul 19, 2020·Cancers·Maria Alba SorollaAnabel Sorolla
Jun 18, 2020·Signal Transduction and Targeted Therapy·Lianlian OuyangYongguang Tao
Jun 30, 2019·Journal of Experimental & Clinical Cancer Research : CR·Rui YangYongguang Tao
Mar 4, 2020·Molecular Cancer·Xinyi ZhangYongguang Tao
Dec 10, 2020·Analytical Cellular Pathology (Amsterdam)·Hui XiaoZhenzhong Liu
Mar 28, 2021·Proceedings of the National Academy of Sciences of the United States of America·Wan-Fu WuJan-Ake Gustafsson
Jul 27, 2021·Journal of Cellular Physiology·Yoon-Beom LeeJae-Bong Park
Oct 6, 2021·The Journal of Clinical Investigation·Wenjing ZhangYang Wang

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