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LACTB Regulates PIK3R3 to Promote Autophagy and Inhibit EMT and Proliferation Through the PI3K/AKT/mTOR Signaling Pathway in Colorectal Cancer

Authors Xu W, Yu M, Qin J, Luo Y, Zhong M

Received 20 February 2020

Accepted for publication 30 May 2020

Published 30 June 2020 Volume 2020:12 Pages 5181—5200


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yong Teng

Wei Xu, Minhao Yu, Jun Qin, Yang Luo, Ming Zhong

Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, People’s Republic of China

Correspondence: Ming Zhong Email

Background: Colorectal cancer (CRC) is one of the most common aggressive malignancies. LACTB functions as a tumor suppressor, and previous findings have demonstrated that LACTB can inhibit epithelial-to-mesenchymal transition (EMT) and proliferation of breast cancer and CRC cells. However, few studies have investigated the roles of LACTB in autophagy and proliferation in CRC. The current study aimed to identify the roles of LACTB in EMT and proliferation associated with autophagy in CRC and to elucidate the probable molecular mechanisms through which LACTB are involved in these processes.
Materials and Methods: Transwell invasion, MTT, transmission electron microscopy, RNA-seq, immunoprecipitation, immunohistochemistry and Western blotting assays were performed to evaluate the migratory, invasive, proliferative and autophagic abilities of CRC cells, and the levels of active molecules involved in PI3K/AKT signaling were examined through Western blotting analysis. In addition, the in vivo function of LACTB was assessed using a tumor xenograft model.
Results: Weaker LACTB expression was found in CRC tissue samples than in nonmalignant tissue samples, and LACTB inhibited cell invasion, migration, and proliferation by promoting autophagy in vitro. Furthermore, the regulatory effects of LACTB on autophagy and EMT were partially attributed to the PI3K/AKT signaling pathway. The in vivo results also showed that LACTB modulated CRC tumorigenesis.
Conclusion: LACTB can regulate the activity of PIK3R3 to influence the level of PI3K, and it also promotes autophagy and inhibits EMT and proliferation in part through the PI3K/AKT/mTOR signaling pathway.

Keywords: colorectal cancer, LACTB, PIK3R3, EMT, proliferation, autophagy

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