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Article

PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway

  • Authors:
    • Wenli Chen
    • Guangli Dai
    • Yike Qian
    • Lian Wen
    • Xueqing He
    • Hui Liu
    • Yunxing Gao
    • Xingli Tang
    • Bohan Dong
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Wannan Medical College, Wuhu, Anhui 241002, P.R. China, Department of Obstetrics and Gynecology, Wuhu Traditional Chinese Medicine Hospital, Wuhu, Anhui 241003, P.R. China, Department of Pharmacy, Wannan Medical College, Wuhu, Anhui 241002, P.R. China, Department of Microbiology and Immunology, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
  • Article Number: 11
    |
    Published online on: November 9, 2021
       https://doi.org/10.3892/or.2021.8222
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Abstract

The phosphatidylinositol‑3‑kinase catalytic subunit α (PIK3CA) gene is mutated in numerous human cancers. This mutation promotes the proliferation of tumor cells; however, the underlying mechanism is still not clear. In the present study, it was revealed that the PIK3CA mutation in colorectal cancer (CRC) HCT116 (MUT) rendered the cells more dependent on glutamine by regulating the glutamic‑pyruvate transaminase 2 (GPT2). The dependence of glutamine increased the proliferation of cells in a normal environment and resistance to a suboptimal environment. Further study revealed that the mutated PIK3CA could regulate GPT2 expression not only through signal transduction molecule 3‑phosphoinositide‑dependent kinase (PDK1) but also through mitogen‑activated protein kinase (MEK) molecules. In HCT116 cells, MEK inhibitor treatment could reduce the expression of GPT2 signaling molecules, thereby inhibiting the proliferation of CRC cells. A new signal transduction pathway, the PI3K/MEK/GPT2 pathway was identified. Based on these findings, MEK and PDK1 inhibitors were combined to inhibit the aforementioned pathway. It was revealed that the combined application of MEK and PDK1 inhibitors could promisingly inhibit the proliferation of MUT compared with the application of PI3K inhibitors, PDK1 inhibitors, or MEK inhibitors alone. In vivo, MEK inhibitors alone and combined inhibitors had stronger tumor‑suppressing effects. There was no significant difference between the PDK1‑inhibitor group and normal group in vivo. Thus, these results indicated that mutated PI3K affected GPT2 mediated by the MEK/PDK1 dual pathway, and that the PI3K/MEK/GPT2 pathway was more important in vivo. Inhibiting MEK and PDK1 concurrently could effectively inhibit the proliferation of CRC cells. Targeting the MEK and PDK1 signaling pathway may provide a novel strategy for the treatment of PIK3CA‑mutated CRC.
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Copy and paste a formatted citation
Spandidos Publications style
Chen W, Dai G, Qian Y, Wen L, He X, Liu H, Gao Y, Tang X and Dong B: PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway. Oncol Rep 47: 11, 2022.
APA
Chen, W., Dai, G., Qian, Y., Wen, L., He, X., Liu, H. ... Dong, B. (2022). PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway. Oncology Reports, 47, 11. https://doi.org/10.3892/or.2021.8222
MLA
Chen, W., Dai, G., Qian, Y., Wen, L., He, X., Liu, H., Gao, Y., Tang, X., Dong, B."PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway". Oncology Reports 47.1 (2022): 11.
Chicago
Chen, W., Dai, G., Qian, Y., Wen, L., He, X., Liu, H., Gao, Y., Tang, X., Dong, B."PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway". Oncology Reports 47, no. 1 (2022): 11. https://doi.org/10.3892/or.2021.8222
Copy and paste a formatted citation
x
Spandidos Publications style
Chen W, Dai G, Qian Y, Wen L, He X, Liu H, Gao Y, Tang X and Dong B: PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway. Oncol Rep 47: 11, 2022.
APA
Chen, W., Dai, G., Qian, Y., Wen, L., He, X., Liu, H. ... Dong, B. (2022). PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway. Oncology Reports, 47, 11. https://doi.org/10.3892/or.2021.8222
MLA
Chen, W., Dai, G., Qian, Y., Wen, L., He, X., Liu, H., Gao, Y., Tang, X., Dong, B."PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway". Oncology Reports 47.1 (2022): 11.
Chicago
Chen, W., Dai, G., Qian, Y., Wen, L., He, X., Liu, H., Gao, Y., Tang, X., Dong, B."PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway". Oncology Reports 47, no. 1 (2022): 11. https://doi.org/10.3892/or.2021.8222
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