Advances in Cancer Drug Targets

Volume: 1

AKT Signaling in Regulating Angiogenesis

Author(s): Bing-Hua Jiang and Ling-Zhi Liu

Pp: 22-50 (29)

DOI: 10.2174/9781608054749113010004

* (Excluding Mailing and Handling)

Abstract

AKT is a central signaling molecule in regulating cell survival, proliferation, tumor growth and angiogenesis. Upstream components of AKT signaling pathway such as PI3K, PTEN, and Ras are commonly mutated in many human cancers. Some miRNAs are also involved in regulating PI3K/AKT signaling pathway. Recently it is found that AKT plays an important role in regulating normal vascularization and pathological angiogenesis. Angiogenesis is required for tumor growth and metastasis when tumor reaches more than 1 mm in diameter. This review focuses on the role and potential mechanism of AKT signaling in regulating angiogenesis. Recent studies have shown that AKT activation is necessary and sufficient to regulate VEGF and HIF-1α expression in human cancer cells. VEGF and HIF-1α are potent inducers of angiogenesis. It was found that AKT activation induces VEGF and HIF-1α expression through its two downstream molecules HDM2 and p70S6K1. On the other hand, AKT transmits the upstream signals from growth factors, cytokines, heavy metals, and oncogenes for regulating VEGF and HIF-1α expression in human cancer cells. AKT activation and VEGF expression can be inhibited by different natural products used for cancer prevention. Thus, inhibition of AKT and its downstream targets offers a new approach for targeting angiogenesis, which could be important for the development of new cancer therapeutics in the future.


Keywords: AKT, VEGF, HIF-1, tumor growth, vascularization, and angiogenesis.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873346344 and j.to_ip >=873346344 )) and ((j.from_date <= 1739834804 and j.to_date >= 1739834804 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4780) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873346344 and j.to_ip >=873346344 )) and ((j.from_date <= 1739834804 and j.to_date >= 1739834804 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4780) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873346344 and j.to_ip >=873346344 )) and ((j.from_date <= 1739834804 and j.to_date >= 1739834804 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4780)
      690μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1176 and `b`.`banner_from_date` <= 1739834804 and `b`.`banner_to_date` >= 1739834804 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1176
      • 3: 1739834804
      • 4: 1739834804
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='76505e6b0b3b53dc656a808183c361ad'
      180μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    6Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        n6GucE1tcGaaXu2EqsBA6N92BPBiSxfzZALNTXgv
        uc_cart_id
        76505e6b0b3b53dc656a808183c361ad
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4780" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/4780
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImF1MEVhckxnb0FzTGxnRzdFVzJuREE9PSIsInZhbHVlIjoiR0dUekZlMDBadmU0a3lpZ0J6SFMrQWhlZkZWQlBnMG9wVk1FUSswbzlQZHBiYzlLUVYxNURMUHJ4RFcrdFZjSCIsIm1hYyI6ImY0YmU3OWFjZGU3M2Q4MjFlYTdkN2QyMTI0ZDFhMTcxNjhhZjZlNjA2NTYwM2FlYTM3M2E1NjhkZDRiMTljOGUiLCJ0YWciOiIifQ%3D%3D; XSRF-TOKEN=eyJpdiI6ImdpaDBWdEdERmhxL3VQN094dDgyUkE9PSIsInZhbHVlIjoiZFNud2xCOTRNdjRSektMR3VVeHlxYWZBbVBBWEtNR1lCeDFhcGZPUmovMmUrbVNVZXpiOEZsVFJWSXozNXdONGVJc1laK2hodUd0MWp5NllJNUhFMzdEQlZWSGJyekNNbGpCOE9MeVJJNTREK2UrdkJSVzZXTlpOcUFqQ2FDOFciLCJtYWMiOiJkODBkYmYyMTM4NzIzZDJlMDg3OTRiZDE3ZDY3MzZkMWJmYTk3MzRlZDNkZDBiODlmZGYzNjU3MDdlZDBmNGVmIiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6IjlENFp3ZVozd2Q0ekRjbEJPZ2dmMFE9PSIsInZhbHVlIjoia3BTRURidDUxaTNBTEVhbzFwejB0YUxJc1F5V3Jmbmd0YUpOd3IzNHIyY0VsQytNRXRFSGR4dTVqMnFWTUp1R1hOZUFtOUh2SDNmYTcwY1lpdUtRekNIcUtCREVGdGNFVG1uRU5TTUxyN0dsektSN3poSFB0YUJFL1pBQVl3b1EiLCJtYWMiOiI4OGQ3NzIxY2FjZWZmOTFkZDI0MWZmNTRlMzMxMGRjM2RmOTRiYTg3YzljNTI0YmM3OWE5ZjkwMjlhMGRhOWRkIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImF1MEVhckxnb0FzTGxnRzdFVzJuREE9PSIsInZhbHVlIjoiR0dUekZlMDBadmU0a3lpZ0J6SFMrQWhlZkZWQlBnMG9wVk1FUSswbzlQZHBiYzlLUVYxNURMUHJ4RFcrdFZjSCIs" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        array:5 [ "_token" => "n6GucE1tcGaaXu2EqsBA6N92BPBiSxfzZALNTXgv" "uc_cart_id" => "76505e6b0b3b53dc656a808183c361ad" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4780" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:26:44GET/chapter/4780112198