Expression of a splicing variant of the CADM1 specific to small cell lung cancer

Shinji Kikuchi, Miwako Iwai, Mika Sakurai-Yageta, Yumi Tsuboi, Takeshi Ito, Tomoko Maruyama, Hitoshi Tsuda, Yae Kanai, Masataka Onizuka, Yukio Sato, Yoshinori Murakami

Research output: Contribution to journalArticle

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Abstract

CADM1, a member of the immunoglobulin superfamily cell adhesion molecule, acts as a tumor suppressor in a variety of human cancers. CADM1 is also ectopically expressed in adult T-cell leukemia (ATL), conferring an invasive phenotype characteristic to ATL. Therefore, CADM1 plays dual roles in human oncogenesis. Here, we investigate the roles of CADM1 in small cell lung cancer (SCLC). Immunohistochemistry demonstrates that 10 of 35 (29%) primary SCLC tumors express CADM1 protein. Western blotting and RT-PCR analyses reveal that CADM1 is significantly expressed in 11 of 14 SCLC cells growing in suspension cultures but in neither of 2 SCLC cells showing attached growth to plastic dishes, suggesting that CADM1 is involved in anchorage-independent growth in SCLC. In the present study, we demonstrate that SCLC expresses a unique splicing variant of CADM1 (variant 8/9) containing additional extracellular fragments corresponding to exon 9 in addition to variant 8, a common isoform in epithelia. Variant 8/9 of CADM1 is almost exclusively observed in SCLC and testis, although this variant protein localizes along the membrane and shows similar cell aggregation activity to variant 8. Interestingly, both variant 8/9 and variant 8 of CADM1 show enhanced tumorigenicity in nude mice when transfected into SBC5, a SCLC cell lacking CADM1. Inversely, suppression of CADM1 expression by shRNA reduced spheroid-like cell aggregation of NCI-H69, an SCLC cell expressing a high amount of CADM1. These findings suggest that CADM1 enhances the malignant features of SCLC, as is observed in ATL, and could provide a molecular marker specific to SCLC.

Original languageEnglish
Pages (from-to)1051-1057
Number of pages7
JournalCancer Science
Volume103
Issue number6
DOIs
Publication statusPublished - 2012 Jun
Externally publishedYes

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Small Cell Lung Carcinoma
Adult T Cell Leukemia Lymphoma
Cell Aggregation
Neoplasms
Testicular Neoplasms
Cell Adhesion Molecules
Growth
Nude Mice
Small Interfering RNA
Plastics
Immunoglobulins
Exons
Suspensions
Protein Isoforms
Carcinogenesis
Proteins
Epithelium
Western Blotting
Immunohistochemistry
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kikuchi, S., Iwai, M., Sakurai-Yageta, M., Tsuboi, Y., Ito, T., Maruyama, T., ... Murakami, Y. (2012). Expression of a splicing variant of the CADM1 specific to small cell lung cancer. Cancer Science, 103(6), 1051-1057. https://doi.org/10.1111/j.1349-7006.2012.02277.x

Expression of a splicing variant of the CADM1 specific to small cell lung cancer. / Kikuchi, Shinji; Iwai, Miwako; Sakurai-Yageta, Mika; Tsuboi, Yumi; Ito, Takeshi; Maruyama, Tomoko; Tsuda, Hitoshi; Kanai, Yae; Onizuka, Masataka; Sato, Yukio; Murakami, Yoshinori.

In: Cancer Science, Vol. 103, No. 6, 06.2012, p. 1051-1057.

Research output: Contribution to journalArticle

Kikuchi, S, Iwai, M, Sakurai-Yageta, M, Tsuboi, Y, Ito, T, Maruyama, T, Tsuda, H, Kanai, Y, Onizuka, M, Sato, Y & Murakami, Y 2012, 'Expression of a splicing variant of the CADM1 specific to small cell lung cancer', Cancer Science, vol. 103, no. 6, pp. 1051-1057. https://doi.org/10.1111/j.1349-7006.2012.02277.x
Kikuchi S, Iwai M, Sakurai-Yageta M, Tsuboi Y, Ito T, Maruyama T et al. Expression of a splicing variant of the CADM1 specific to small cell lung cancer. Cancer Science. 2012 Jun;103(6):1051-1057. https://doi.org/10.1111/j.1349-7006.2012.02277.x
Kikuchi, Shinji ; Iwai, Miwako ; Sakurai-Yageta, Mika ; Tsuboi, Yumi ; Ito, Takeshi ; Maruyama, Tomoko ; Tsuda, Hitoshi ; Kanai, Yae ; Onizuka, Masataka ; Sato, Yukio ; Murakami, Yoshinori. / Expression of a splicing variant of the CADM1 specific to small cell lung cancer. In: Cancer Science. 2012 ; Vol. 103, No. 6. pp. 1051-1057.
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