COL6A6 interacted with P4HA3 to suppress the growth and metastasis of pituitary adenoma via blocking PI3K-Akt pathway.

Ruiqing Long,Hualin Yu,Jinghui Li,Zhuohui Liu

doi:10.18632/aging.102300

Ruiqing Long, Hualin Yu + Show 2 more

Open Access

https://doi.org/10.18632/aging.102300

Copy DOI

Abstract

The role and mechanism of collagen type VI alpha 6 (COL6A6) on tumor growth and metastasis in pituitary adenoma (PA) was determined. COL6A6 was downregulated in PA tissues and cell lines, which was negatively associated with the expression of prolyl-4-hydroxylase alpha polypeptide III (P4HA3) in the progression of PA. Overexpression of COL6A6 significantly suppressed tumor growth and metastasis capacity in PA. In addition, P4HA3 worked as the upstream of the PI3K-Akt pathway to alleviate the antitumor activity of COL6A6 on the growth and metastasis of both AtT-20 and HP75 cells. Furthermore, the inhibitory effect of COL6A6 on cell proliferation, migration and invasion, and epithelial-mesenchymal transition (EMT) was reversed by P4HA3 overexpression or activation of the PI3K-Akt pathway induced by IGF-1 addition, which provided a new biomarker for clinical PA treatment.

Highlights

Pituitary adenoma (PA) is a kind of common disease in clinical endocrinology and neurology, whose incidence is second only to gliomas and meningiomas and listed in the third place among the intracranial tumors [1, 2]
COL6A6 was downregulated in pituitary adenoma (PA) tissues and cell lines, which was negatively associated with the expression of prolyl-4-hydroxylase alpha polypeptide III (P4HA3) in the progression of PA
The results showed that the top 10 significantly downregulated genes (CSH1, CSH2, DLK1, NKX2-2, CSHL1, PTEN, POU1F1, COL6A6, GH1, and PCK1) associated with tumor metastasis were labeled in Figure 1A, 1B

Summary

Introduction

Pituitary adenoma (PA) is a kind of common disease in clinical endocrinology and neurology, whose incidence is second only to gliomas and meningiomas and listed in the third place among the intracranial tumors [1, 2]. Numerous studies have shown that tumor suppressor genes serve an important role in regulating tumor etiology, development, and prognosis [5,6,7,8]. Discovering and elucidating the action mechanism of related genes is helpful in finding markers that can reflect the specific tumor biological for clinical diagnosis and follow-up study, and can provide theory basis for developing the new therapy of this kind of tumor [9, 10]. Collagen type VI (COL6) is mainly composed of several different alpha chains, which serves an important role in regulating cell proliferation, apoptosis, invasion, and metastasis, epithelial-mesenchymal transition (EMT) and angiogenesis of malignant tumors by the formation of cell microfilament network and interaction with extracellular matrix molecules [11, 12]. The role and mechanism of COL6A6 in cancer progression has not yet clear

Objectives

Methods

Results

Conclusion