br Published by Elsevier B
© 2019 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Lung cancer is the most common cause of malignant tumours world-wide .Of the different types of lung cancer, non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancer cases. The majority of NSCLC cases are diagnosed at later stages with local invasion or distal metastases, consequently leading to poor effectiveness of surgical or
Correspondence to: School of Medicine, Shandong University, No. 44 Wenhua West-Road, Ji Nan, Shandong Province 250012, China.
radiotherapeutic interventions . Therefore, there is an urgent need for further understanding of the mechanism underlying NSCLC onco-genesis to support the development of novel therapeutic interventions. Cancer is the uncontrolled growth of abnormal T16Ainh-A01 anywhere in the body. Proteins that regulate cell proliferation, apoptosis, and invasion are critically involved in the pathogenesis of cancers. Amyloid protein-binding protein 2 (APPBP2) interacts with microtubules and is function-ally associated with beta-amyloid precursor protein transport and/or processing [3,4].Studies have demonstrated that APPBP2 plays a key role in the oncogenesis of numerous types of cancer. For instance, Hirasawa et al. demonstrated that APPBP2 is closely associated with ma-lignant phenotypes of ovarian adenocarcinomas . In breast cancer, APPBP2 expression is significantly upregulated, prompting tumour cell
Research in context
Evidence before this study
APPBP2 interacts with microtubules and is functionally associated with beta-amyloid precursor protein (APP) transport and/or pro-cessing. Microtubules participate in the formation of the spindle during cell division (mitosis) responsible for cell proliferation. APP is a cell surface protein with signal-transducing properties and con-trols cells viability, proliferation, migration, and aggressiveness in various cancers. Based on the regulation of microtubules and APP, APPBP2 is found to be involved in the oncogenesis of various types of cancers, such as breast cancer, ovarian clear cell adeno-carcinomas, desmoplastic medulloblastomas and neuroblasto-mas. However, the effects of APPBP2 on non-small cell lung cancer (NSCLC) remains unclear.
Added value of this study
In this study, the investigators first demonstrate that APPBP2 ex-pression is significantly enhanced in NSCLC tumours relative to tumour-adjacent normal tissues. Then the investigators provide evidence that APPBP2 controls NSCLC cell proliferation, apopto-sis, migration, and invasiveness. Moreover, the investigators dis-covered that PPM1D and SPOP participate in the molecular mechanism underlying the roles of APPBP2 in NSCLC. Taken to-gether, these findings suggest that APPBP2 contributes to NSCLC progression through regulating the PPM1D and SPOP sig-nalling pathways.
Implications of all the available evidence
Targeted therapies show great promise in effectively treating lung cancer patients. Therefore, characterizing and targeting the functionally-relevant molecular aberrations in lung cancer helps to identify new approaches to manage this disease. This research suggests that APPBP2 has a close relationship with NSCLC and contributes to the initiation and progression of NSCLC through regulating the PPM1D and SPOP pathways. Although the implica-tions of APPBP2 in other cancers has been reported, we are the first to clarify the role of APPBP2 in NSCLC and the underlying mo-lecular mechanisms. Therefore, this study provides a novel molec-ular mechanism underlying the oncogenesis of NSCLC and supports APPBP2 as a potential valuable molecular target suitable for diagnosis and therapeutic intervention in NSCLC.
invasion and metastasis .In desmoplastic medulloblastomas and neu-roblastomas, the gene of APPBP2 is amplified with links to cancer initi-ation and progression [7,8]. These findings suggest that APPBP2 is implicated in the occurrence and development of cancers. However, the influence of APPBP2 on lung cancer remains unclear. Elucidating the roles of APPBP2 in NSCLC cells can improve our understanding of the molecular mechanism underlying lung cancer while benefiting the development of targeted therapies to combat NSCLC.
This study confirms the elevated expression of APPBP2 in NSCLC tis-sue compared with normal tumour-adjacent lung tissue. On a cellular level, the investigators demonstrate that APPBP2 promotes cell prolifer-ation, migration, and invasiveness but inhibits cell apoptosis in NSCLC. In this study APPBP2 knockdown consistently reduces the growth of NSCLC xenograft. Moreover, the investigators prove that the level of APPBP2 expression positively correlates with the level of PPM1D and SPOP expression. Also the overexpression of PPM1D as well as SPOP can significantly attenuate the APPBP2-knockdown inhibition of cell proliferation, migration, and invasiveness in NSCLC cells. The