PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting v integrin/FAK/Src signaling in oral squamous cell carcinoma cells.
10.1016/j.apsb.2019.10.005
- Author:
Gulnara TUGUZBAEVA
1
;
Er YUE
2
;
Xi CHEN
2
;
Lina HE
3
;
Xinlei LI
4
;
Jiaming JU
4
;
Ying QIN
4
;
Valentin PAVLOV
1
;
Yanjie LU
2
;
Wenting JIA
2
;
Yunlong BAI
2
;
Yumei NIU
3
;
Baofeng YANG
2
Author Information
1. Central Laboratory of Scientific Research, Bashkir State Medical University, Ufa 450008, Russian Federation.
2. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.
3. Department of Endodontics, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
4. Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China.
- Publication Type:Journal Article
- Keywords:
CTC, circulating tumor cell;
Collective migration;
ECM, extracellular matrix;
EMT, epithelial–mesenchymal transition;
FAK, focal adhesion kinase;
HNSCC, head and neck squamous cell carcinoma;
MCA, multicellular aggregates;
Metastasis;
OSCC, oral squamous cell carcinoma;
Oral squamous cell carcinoma;
RGD;
RGD, Arg-Gly-Asp;
Tumor cell clusters;
poly-HEMA, polyhydroxylethyl-methacrylate;
αv integrin/FAK/RC signaling
- From:
Acta Pharmaceutica Sinica B
2019;9(6):1163-1173
- CountryChina
- Language:English
-
Abstract:
Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.
