Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma.

Bo You,Zhifeng Gu,Yiwen You,Si Shi,Xiaoyi Shao,Ying Shan,Haosheng Ni,Xiaolei Cao

doi:10.18632/oncotarget.7274

Abstract

HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment.

Highlights

Nasopharyngeal carcinoma (NPC), a squamous epithelial cancer arising from the lateral wall surface of the nasopharynx, is the most common head and neck cancer, with an incidence of 30–80/100,000 each year in China [1, 2]
To evaluate whether exosomal HS1-associated protein X-1 (HAX-1) was critical for modulating exosomal induction of proliferation, migration and angiogenesis, human umbilical vein endothelial cells (HUVECs) were stimulated with exosomes with different levels of HAX-1 protein
Western blot confirmed that these exosomes contained different levels of HAX-1 protein (Figure 9A–9B)

Summary

Introduction

Nasopharyngeal carcinoma (NPC), a squamous epithelial cancer arising from the lateral wall surface of the nasopharynx, is the most common head and neck cancer, with an incidence of 30–80/100,000 each year in China [1, 2]. HS1-associated protein X-1 (HAX-1) is involved in a variety of important physiological processes including the regulation of apoptosis, cell motility, endocytosis, and interactions with the 3′untranslated regions (3′UTR) of a variety of proteins such as vimentin and DNA polymerase β [6,7,8,9,10,11]. While it is predominantly localized in the mitochondria, HAX-1 can be found at endoplasmic reticulum and nuclear membrane [12]. HAX-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin αVβ6 [13]

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Results

Conclusion