PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting αv integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Gulnara Tuguzbaeva; Er Yue; Xi Chen; Lina He; Xinlei Li; Jiaming Ju; Ying Qin; Valentin Pavlov; Yanjie Lu; Wenting Jia; Yunlong Bai; Yumei Niu; Baofeng Yang

Acta Pharmaceutica Sinica B (Nov 2019)

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting αv integrin/FAK/Src signaling in oral squamous cell carcinoma cells

Gulnara Tuguzbaeva,
Er Yue,
Xi Chen,
Lina He,
Xinlei Li,
Jiaming Ju,
Ying Qin,
Valentin Pavlov,
Yanjie Lu,
Wenting Jia,
Yunlong Bai,
Yumei Niu,
Baofeng Yang

Affiliations

Gulnara Tuguzbaeva: Central Laboratory of Scientific Research, Bashkir State Medical University, Ufa 450008, Russian Federation; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China; Department of Endodontics, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Department of Orthopedic Dentistry and Maxillofacial Surgery, Bashkir State Medical University, Ufa 450008, Russian Federation
Er Yue: 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
Xi Chen: 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
Lina He: Department of Endodontics, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, China
Xinlei Li: Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Jiaming Ju: Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Ying Qin: Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Valentin Pavlov: Central Laboratory of Scientific Research, Bashkir State Medical University, Ufa 450008, Russian Federation
Yanjie Lu: 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; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Wenting Jia: 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; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Yunlong Bai: 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; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Yumei Niu: Department of Endodontics, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Corresponding authors. Tel./fax: +86 451 86671354.
Baofeng Yang: 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; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China; Corresponding authors. Tel./fax: +86 451 86671354.

Journal volume & issue: Vol. 9, no. 6
pp. 1163 – 1173

Abstract

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Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), αv integrin is a crucial mediator of multicellular clustering and collective movement in vitro; 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 in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv 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 αv 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 in vitro. Overall, these results suggest that PEP06 polypeptide 30 inhibiting αv 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. KEY WORDS: Oral squamous cell carcinoma, Tumor cell clusters, Collective migration, Metastasis, αv integrin/FAK/RC signaling, RGD

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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