T-lymphoma invasion and metastasis 1 promotes invadopodia formation and is regulated by the PI3K/Akt signaling pathway in hepatocellular carcinoma

Baolin Wang; Bowen Zheng; Li Cao; Kexi Liao; Deng Huang; Yujun Zhang; Yan Jiang; Shuguo Zheng

doi:10.1016/j.yexcr.2021.112806

T-lymphoma invasion and metastasis 1 promotes invadopodia formation and is regulated by the PI3K/Akt signaling pathway in hepatocellular carcinoma

Exp Cell Res. 2021 Oct 15;407(2):112806. doi: 10.1016/j.yexcr.2021.112806. Epub 2021 Sep 4.

Authors

Baolin Wang¹, Bowen Zheng², Li Cao², Kexi Liao², Deng Huang³, Yujun Zhang², Yan Jiang², Shuguo Zheng⁴

Affiliations

¹ Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Department of Surgery, The 63650th Troop Hospital of the Chinese People's Liberation Army, Urumqi, Xinjinag, 841700, China.
² Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
³ Department of Hepatobiliary, General Hospital of Tibet Military Command Area, Lhasa, Tibet, 850000, China.
⁴ Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: shuguozh@tmmu.edu.cn.

PMID: 34487727
DOI: 10.1016/j.yexcr.2021.112806

Abstract

At present, there are still many poorly understood aspects of the mechanisms underlying hepatocellular carcinoma (HCC) invasion and metastasis. Invadopodia are important structures for cancer cell invasion and metastasis. We determined that high T-lymphoma invasion and metastasis 1 (Tiam1) expression is associated with HCC invasion and metastasis and poor patient prognosis after surgery. Gain- and loss-of-function studies confirmed that Tiam1 promotes invadopodia formation in HCC by activating Rac1. A series of biochemical experiments confirmed that this effect is regulated by the PI3K/Akt signaling pathway. We also confirmed that PIP2 facilitates this effect. In summary, these findings reveal that Tiam1 plays an important role in invadopodia formation in HCC.

Keywords: Hepatocellular carcinoma; Invadopodia formation; PI3K/Akt; PIP2; T-lymphoma invasion and metastasis 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology*
Cell Movement
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic*
Humans
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Male
Mice
Mice, Nude
Middle Aged
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism*
Podosomes / metabolism
Podosomes / pathology*
Prognosis
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
Survival Rate
T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics
T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

T-Lymphoma Invasion and Metastasis-inducing Protein 1
TIAM1 protein, human
Proto-Oncogene Proteins c-akt