Metastatic potential of lung squamous cell carcinoma associated with HSPC300 through its interaction with WAVE2.
The small protein, HSPC300 (haematopoietic stem/progenitor cell protein 300), is associated with reorganization of actin filaments and cell movement, but its activity has not been reported in human cancer cells. Here, we investigated the association of HSPC300 expression with clinical features of lung squamous cell carcinoma. High levels of HSPC300 protein were detected in 84.1% of tumour samples, and in 30.8% of adjacent morphologically normal tissues. The number of primary tumours with elevated HSPC300 levels was significantly higher in primary tumours with lymph node metastases as opposed to those without, and also in tumours from patients with more advanced disease. HSPC300 modulates the morphology and motility of cells, as siRNA knockdown caused the reorganization of actin filaments, decreased the formation of pseudopodia, and inhibited the migration of a lung cancer cell line. We further showed that HSPC300 interacted with the WAVE2 protein, and HSPC300 silencing resulted in the degradation of WAVE2 in vitro. HSPC300 and WAVE2 were co-expressed in approximately 85.7% of primary tumours with lymph node metastases. We hypothesize that HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2.
Cai
Xiongwei
X
State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
Xiao
Ting
T
James
Sharon Y
SY
Da
Jiping
J
Lin
Dongmei
D
Liu
Yu
Y
Zheng
Yang
Y
Zou
Shuangmei
S
Di
Xuebing
X
Guo
Suping
S
Han
Naijun
N
Lu
Yong-Jie
YJ
Cheng
Shujun
S
Gao
Yanning
Y
Zhang
Kaitai
K
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D011485:Protein Binding; D011554:Pseudopodia / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*
C519848:BRK1 protein, human; D003598:Cytoskeletal Proteins; D034741:RNA, Small Interfering; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family