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Int J Biol Sci 2023; 19(9):2817-2834. doi:10.7150/ijbs.79949 This issue Cite

Research Paper

Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer

Xiangdong Tian#, Yuchao He#, Lisha Qi#, Dongming Liu#, Dejun Zhou, Yun Liu, Wenchen Gong, Zhiqiang Han, Yuren Xia, Hua Li, Jiefu Wang, Kangwei Zhu, Lu Chen✉, Hua Guo✉, Qiang Zhao✉

National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
#These authors contributed equally to this work.

✉ Corresponding author: Qiang Zhao, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China, Tel.: +86 22 23537796, fax: +86 22 23537796, E-mail: qiangzhao169com; Hua Guo, Tianjin Medical University Cancer Institute and More

Citation:
Tian X, He Y, Qi L, Liu D, Zhou D, Liu Y, Gong W, Han Z, Xia Y, Li H, Wang J, Zhu K, Chen L, Guo H, Zhao Q. Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer. Int J Biol Sci 2023; 19(9):2817-2834. doi:10.7150/ijbs.79949. https://www.ijbs.com/v19p2817.htm
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Abstract

Graphic abstract

Dormant cancer cells account for cancer recurrence, distant metastasis and drug resistance which lead to poor prognosis in colorectal cancer (CRC). However, little is known about the molecular mechanisms regulating tumor cell dormancy and how to eliminate dormant cancer cells. Recent studies indicate autophagy affects dormant tumor cell survival. Here, we found that polo-like kinases 4 (PLK4), a central regulator of the cell cycle and proliferation, plays a crucial role in regulating CRC cells dormancy both in vitro and in vivo. Downregulation of PLK4 induced dormancy and inhibited migration and invasion in different CRC cell lines. Clinically, PLK4 expression was correlated with the dormancy markers (Ki67, p-ERK, p-p38) and late recurrence in CRC tissues. Mechanistically, downregulation of PLK4 induced autophagy contributed to restoring phenotypically aggressive tumor cells to a dormant state through the MAPK signaling pathway, and inhibition of autophagy would trigger apoptosis of dormant cells. Our findings reveal that downregulation of PLK4-induced autophagy contributes to tumor dormancy and autophagy inhibition leads to apoptosis of CRC dormant cells. Our study is the first to report that downregulation PLK4 induced autophagy is an early event in CRC dormancy and highlights autophagy inhibitor as a potential therapeutic target for dormant cell elimination.

Keywords: autophagy, dormancy, PLK4, colorectal cancer

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APA
Tian, X., He, Y., Qi, L., Liu, D., Zhou, D., Liu, Y., Gong, W., Han, Z., Xia, Y., Li, H., Wang, J., Zhu, K., Chen, L., Guo, H., Zhao, Q. (2023). Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer. International Journal of Biological Sciences, 19(9), 2817-2834. https://doi.org/10.7150/ijbs.79949.

ACS
Tian, X.; He, Y.; Qi, L.; Liu, D.; Zhou, D.; Liu, Y.; Gong, W.; Han, Z.; Xia, Y.; Li, H.; Wang, J.; Zhu, K.; Chen, L.; Guo, H.; Zhao, Q. Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer. Int. J. Biol. Sci. 2023, 19 (9), 2817-2834. DOI: 10.7150/ijbs.79949.

NLM
Tian X, He Y, Qi L, Liu D, Zhou D, Liu Y, Gong W, Han Z, Xia Y, Li H, Wang J, Zhu K, Chen L, Guo H, Zhao Q. Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer. Int J Biol Sci 2023; 19(9):2817-2834. doi:10.7150/ijbs.79949. https://www.ijbs.com/v19p2817.htm

CSE
Tian X, He Y, Qi L, Liu D, Zhou D, Liu Y, Gong W, Han Z, Xia Y, Li H, Wang J, Zhu K, Chen L, Guo H, Zhao Q. 2023. Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer. Int J Biol Sci. 19(9):2817-2834.

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