SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis

Dan-Dan Hu; Hai-Ling Chen; Li-Ming Lou; Hong Zhang; Guo-Liang Yang

doi:10.1042/BSR20194335

SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis

Biosci Rep. 2020 Feb 28;40(2):BSR20194335. doi: 10.1042/BSR20194335.

Authors

Dan-Dan Hu¹, Hai-Ling Chen², Li-Ming Lou¹, Hong Zhang¹, Guo-Liang Yang³

Affiliations

¹ Department of Respiratory Medicine, Zhejiang Provincial Zhongshan Hospital, The Third Affiliated Hospital of Zhejiang Chinese Medical University, 310000, Zhejiang Province, China.
² Department of Respiratory Medicine, Guangxing Hospital, The Affiliated Hospital of Zhejiang Chinese Medical University, 310000, Zhejiang Province, China.
³ Intern medicine of Oncology, Zhejiang Integrated Trational and Western Medicine Hospital, 310000, Zhejiang Province, China.

Abstract

The processes that lead to lung adenocarcinoma (LUAD) metastasis are poorly characterized. Spindle and kinetochore associated complex subunit 3 (SKA3) plays a key role in cervical cancer development, but its contribution to LUAD is unknown. Here, we found that SKA3 is overexpressed in LUAD and its expression correlates with lymph node metastasis and poor prognosis. SKA3 silencing experiments identified SKA3 as an oncogene that promotes the metastasis of LUAD cell lines and tissues. SKA3 was found to induce the expression of matrix metalloproteinase (MMP)-2, -7, and -9, which activate PI3K-AKT. SKA3 was also found to bind and activate EGFR to activate PI3K-AKT. In summary, we identify a role for SKA3 in LUAD metastasis through its ability to bind EFGR and activate PI3K-AKT signaling.

Keywords: EGFR; LUAD; PI3K-AKT; SKA3; cancer; metastasis.

Publication types

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

MeSH terms

Adenocarcinoma of Lung / enzymology*
Adenocarcinoma of Lung / genetics
Adenocarcinoma of Lung / secondary
Animals
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Line, Tumor
Cell Movement*
ErbB Receptors / metabolism
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms / enzymology*
Lung Neoplasms / genetics
Lung Neoplasms / pathology
Lymphatic Metastasis
Male
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 7 / genetics
Matrix Metalloproteinase 7 / metabolism
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism
Mice, Nude
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
Phosphatidylinositol 3-Kinase / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction

Substances

Cell Cycle Proteins
Microtubule-Associated Proteins
Ska3 protein, human
Phosphatidylinositol 3-Kinase
EGFR protein, human
ErbB Receptors
Proto-Oncogene Proteins c-akt
MMP7 protein, human
Matrix Metalloproteinase 7
MMP2 protein, human
Matrix Metalloproteinase 2
MMP9 protein, human
Matrix Metalloproteinase 9