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Int J Biol Sci 2024; 20(6):2202-2218. doi:10.7150/ijbs.82361 This issue Cite

Research Paper

PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer

Zi-Jia Huang1†, Yang-Jia Li1†, Jie Yang1†, Lei Huang2, Qian Zhao1, Yi-Fan Lu1, Yang Hu1, Wei-Xia Zhang1, Jun-Ze Liang1, Jinghua Pan3, Yun-Long Pan3, Qing-Yu He1✉, Yang Wang1✉

1. MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
2. Department of Molecular, Cell and Cancer Biology, Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
3. Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
† These authors contribute equally to this work.

✉ Corresponding authors: wangyang0507edu.cn; tqyheedu.cn.

Citation:
Huang ZJ, Li YJ, Yang J, Huang L, Zhao Q, Lu YF, Hu Y, Zhang WX, Liang JZ, Pan J, Pan YL, He QY, Wang Y. PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer. Int J Biol Sci 2024; 20(6):2202-2218. doi:10.7150/ijbs.82361. https://www.ijbs.com/v20p2202.htm
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Abstract

Graphic abstract

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.

Keywords: PTPLAD1, PHB, Raf, ERK, Colorectal cancer, Metastasis, Epithelial-to-mesenchymal transition, Mitofission

Citation styles

APA
Huang, Z.J., Li, Y.J., Yang, J., Huang, L., Zhao, Q., Lu, Y.F., Hu, Y., Zhang, W.X., Liang, J.Z., Pan, J., Pan, Y.L., He, Q.Y., Wang, Y. (2024). PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer. International Journal of Biological Sciences, 20(6), 2202-2218. https://doi.org/10.7150/ijbs.82361.

ACS
Huang, Z.J.; Li, Y.J.; Yang, J.; Huang, L.; Zhao, Q.; Lu, Y.F.; Hu, Y.; Zhang, W.X.; Liang, J.Z.; Pan, J.; Pan, Y.L.; He, Q.Y.; Wang, Y. PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer. Int. J. Biol. Sci. 2024, 20 (6), 2202-2218. DOI: 10.7150/ijbs.82361.

NLM
Huang ZJ, Li YJ, Yang J, Huang L, Zhao Q, Lu YF, Hu Y, Zhang WX, Liang JZ, Pan J, Pan YL, He QY, Wang Y. PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer. Int J Biol Sci 2024; 20(6):2202-2218. doi:10.7150/ijbs.82361. https://www.ijbs.com/v20p2202.htm

CSE
Huang ZJ, Li YJ, Yang J, Huang L, Zhao Q, Lu YF, Hu Y, Zhang WX, Liang JZ, Pan J, Pan YL, He QY, Wang Y. 2024. PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer. Int J Biol Sci. 20(6):2202-2218.

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