Two novel human NUMB isoforms provide a potential link between development and cancer
<p>Abstract</p> <p>We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-12-01
|
| Series: | Neural Development |
| Online Access: | http://www.neuraldevelopment.com/content/5/1/31 |
| _version_ | 1811277459147980800 |
|---|---|
| author | Prudovsky Igor Adams Tamara L Cowling Rebecca Kubu Chris Tremblay Roger Bani-Yaghoub Mahmud Karaczyn Aldona Spicer Douglas Friesel Robert Vary Calvin Verdi Joseph M |
| author_facet | Prudovsky Igor Adams Tamara L Cowling Rebecca Kubu Chris Tremblay Roger Bani-Yaghoub Mahmud Karaczyn Aldona Spicer Douglas Friesel Robert Vary Calvin Verdi Joseph M |
| author_sort | Prudovsky Igor |
| collection | DOAJ |
| description | <p>Abstract</p> <p>We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells. RT-PCR and luciferase assays demonstrate that NUMB5 and NUMB6 are less antagonistic to NOTCH signaling than other NUMB isoforms. Immunocytochemistry analyses show that NUMB5 and NUMB6 interact and complex with CDC42, vimentin and the CDC42 regulator IQGAP1 (IQ (motif) GTPase activating protein 1). Furthermore, the ectopic expression of NUMB5 and NUMB6 induces the formation of lamellipodia (NUMB5) and filopodia (NUMB6) in a CDC42- and RAC1-dependent manner. These results are complemented by <it>in vitro </it>and <it>in vivo </it>studies, demonstrating that NUMB5 and NUMB6 alter the migratory behavior of cells. Together, these novel isoforms may play a role in further understanding the NUMB function in development and cancer.</p> |
| first_indexed | 2024-04-13T00:16:58Z |
| format | Article |
| id | doaj.art-80cded19b4e54829a01c00a2da4e8bcb |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-04-13T00:16:58Z |
| publishDate | 2010-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-80cded19b4e54829a01c00a2da4e8bcb2022-12-22T03:10:55ZengBMCNeural Development1749-81042010-12-01513110.1186/1749-8104-5-31Two novel human NUMB isoforms provide a potential link between development and cancerPrudovsky IgorAdams Tamara LCowling RebeccaKubu ChrisTremblay RogerBani-Yaghoub MahmudKaraczyn AldonaSpicer DouglasFriesel RobertVary CalvinVerdi Joseph M<p>Abstract</p> <p>We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells. RT-PCR and luciferase assays demonstrate that NUMB5 and NUMB6 are less antagonistic to NOTCH signaling than other NUMB isoforms. Immunocytochemistry analyses show that NUMB5 and NUMB6 interact and complex with CDC42, vimentin and the CDC42 regulator IQGAP1 (IQ (motif) GTPase activating protein 1). Furthermore, the ectopic expression of NUMB5 and NUMB6 induces the formation of lamellipodia (NUMB5) and filopodia (NUMB6) in a CDC42- and RAC1-dependent manner. These results are complemented by <it>in vitro </it>and <it>in vivo </it>studies, demonstrating that NUMB5 and NUMB6 alter the migratory behavior of cells. Together, these novel isoforms may play a role in further understanding the NUMB function in development and cancer.</p>http://www.neuraldevelopment.com/content/5/1/31 |
| spellingShingle | Prudovsky Igor Adams Tamara L Cowling Rebecca Kubu Chris Tremblay Roger Bani-Yaghoub Mahmud Karaczyn Aldona Spicer Douglas Friesel Robert Vary Calvin Verdi Joseph M Two novel human NUMB isoforms provide a potential link between development and cancer Neural Development |
| title | Two novel human NUMB isoforms provide a potential link between development and cancer |
| title_full | Two novel human NUMB isoforms provide a potential link between development and cancer |
| title_fullStr | Two novel human NUMB isoforms provide a potential link between development and cancer |
| title_full_unstemmed | Two novel human NUMB isoforms provide a potential link between development and cancer |
| title_short | Two novel human NUMB isoforms provide a potential link between development and cancer |
| title_sort | two novel human numb isoforms provide a potential link between development and cancer |
| url | http://www.neuraldevelopment.com/content/5/1/31 |
| work_keys_str_mv | AT prudovskyigor twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT adamstamaral twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT cowlingrebecca twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT kubuchris twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT tremblayroger twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT baniyaghoubmahmud twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT karaczynaldona twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT spicerdouglas twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT frieselrobert twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT varycalvin twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer AT verdijosephm twonovelhumannumbisoformsprovideapotentiallinkbetweendevelopmentandcancer |