PLOD2 Is Essential to Functional Activation of Integrin β1 for Invasion/Metastasis in Head and Neck Squamous Cell Carcinomas
Identifieur interne : 000083 ( an2020/Analysis ); précédent : 000082; suivant : 000084PLOD2 Is Essential to Functional Activation of Integrin β1 for Invasion/Metastasis in Head and Neck Squamous Cell Carcinomas
Auteurs : Yushi Ueki [Japon] ; Ken Saito [Japon] ; Hidekazu Iioka [Japon] ; Izumi Sakamoto [Japon] ; Yasuhiro Kanda [Japon] ; Masakiyo Sakaguchi [Japon] ; Arata Horii [Japon] ; Eisaku Kondo [Japon]Source :
- iScience [ 2589-0042 ] ; 2020.
Abstract
Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis
Url:
DOI: 10.1016/j.isci.2020.100850
PubMed: 32058962
PubMed Central: 6997870
Affiliations:
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wicri:level="1"><nlm:aff id="aff1">Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation></author><author><name sortKey="Saito, Ken" sort="Saito, Ken" uniqKey="Saito K" first="Ken" last="Saito">Ken Saito</name><affiliation wicri:level="1"><nlm:aff id="aff1">Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation></author><author><name sortKey="Iioka, Hidekazu" sort="Iioka, Hidekazu" uniqKey="Iioka H" first="Hidekazu" last="Iioka">Hidekazu Iioka</name><affiliation wicri:level="1"><nlm:aff id="aff1">Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation></author><author><name sortKey="Sakamoto, Izumi" sort="Sakamoto, Izumi" uniqKey="Sakamoto I" first="Izumi" last="Sakamoto">Izumi Sakamoto</name><affiliation wicri:level="1"><nlm:aff id="aff3">ACROSCALE Inc., Kokubun-cho, Aoba-ku, Sendai, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>ACROSCALE Inc., Kokubun-cho, Aoba-ku, Sendai</wicri:regionArea><wicri:noRegion>Sendai</wicri:noRegion></affiliation></author><author><name sortKey="Kanda, Yasuhiro" sort="Kanda, Yasuhiro" uniqKey="Kanda Y" first="Yasuhiro" last="Kanda">Yasuhiro Kanda</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation></author><author><name sortKey="Sakaguchi, Masakiyo" sort="Sakaguchi, Masakiyo" uniqKey="Sakaguchi M" first="Masakiyo" last="Sakaguchi">Masakiyo Sakaguchi</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Kita-ku, Okayama, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Kita-ku, Okayama</wicri:regionArea><wicri:noRegion>Okayama</wicri:noRegion></affiliation></author><author><name sortKey="Horii, Arata" sort="Horii, Arata" uniqKey="Horii A" first="Arata" last="Horii">Arata Horii</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation></author><author><name sortKey="Kondo, Eisaku" sort="Kondo, Eisaku" uniqKey="Kondo E" first="Eisaku" last="Kondo">Eisaku Kondo</name><affiliation wicri:level="1"><nlm:aff id="aff1">Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Chuo-ku, Niigata</wicri:regionArea><wicri:noRegion>Niigata</wicri:noRegion></affiliation></author></analytic><series><title level="j">iScience</title><idno type="eISSN">2589-0042</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis <italic>in vivo</italic>, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bonner, J A" uniqKey="Bonner J">J.A. 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Root</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Ueki, Yushi" sort="Ueki, Yushi" uniqKey="Ueki Y" first="Yushi" last="Ueki">Yushi Ueki</name></noRegion><name sortKey="Horii, Arata" sort="Horii, Arata" uniqKey="Horii A" first="Arata" last="Horii">Arata Horii</name><name sortKey="Iioka, Hidekazu" sort="Iioka, Hidekazu" uniqKey="Iioka H" first="Hidekazu" last="Iioka">Hidekazu Iioka</name><name sortKey="Kanda, Yasuhiro" sort="Kanda, Yasuhiro" uniqKey="Kanda Y" first="Yasuhiro" last="Kanda">Yasuhiro Kanda</name><name sortKey="Kondo, Eisaku" sort="Kondo, Eisaku" uniqKey="Kondo E" first="Eisaku" last="Kondo">Eisaku Kondo</name><name sortKey="Saito, Ken" sort="Saito, Ken" uniqKey="Saito K" first="Ken" last="Saito">Ken Saito</name><name sortKey="Sakaguchi, Masakiyo" sort="Sakaguchi, Masakiyo" uniqKey="Sakaguchi M" first="Masakiyo" last="Sakaguchi">Masakiyo Sakaguchi</name><name sortKey="Sakamoto, Izumi" sort="Sakamoto, Izumi" uniqKey="Sakamoto I" first="Izumi" last="Sakamoto">Izumi Sakamoto</name><name sortKey="Ueki, Yushi" sort="Ueki, Yushi" uniqKey="Ueki Y" first="Yushi" last="Ueki">Yushi Ueki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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