Exploring STK3 in Melanoma: a Systematic Review of Signaling Networks and Therapeutic Opportunities

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2024 Nov 22

PMID 39576434

Authors

Maryam Khanahmadi

Mohsen Ebrahimi Fard

Matin Baghani

Maryam Shayan

Moein Baghani

Affiliations

Soon will be listed here.

Abstract

Melanoma is an aggressive cancer that disregards both the MAPK and Hippo signaling pathways. This systematic review explores STK3 function in the Hippo pathway to regulate networks and its therapeutic potential in melanoma. From 1991 to 2024, we studied how STK3 interacts with the MAPK/ERK pathway to promote apoptosis and inhibit tumor growth. STK3 controls cell growth, apoptosis, and metastasis via the Hippo and MAPK pathways. It is a melanoma tumor suppressor. Some ways to target STK3 are to directly activate it, stop downstream effectors like YAP/TAZ from working, or use existing BRAF inhibitors together with other methods. Despite advancements, challenges in STK3 drug development persist, warranting further investigation. This review examined the role of STK3 in the development of melanoma and identified potential vulnerabilities for therapeutic intervention.

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References

La Porta C . Drug resistance in melanoma: new perspectives. Curr Med Chem. 2007; 14(4):387-91. DOI: 10.2174/092986707779941078. View

Garnett M, Marais R . Guilty as charged: B-RAF is a human oncogene. Cancer Cell. 2004; 6(4):313-9. DOI: 10.1016/j.ccr.2004.09.022. View

Feng R, Gong J, Wu L, Wang L, Zhang B, Liang G . MAPK and Hippo signaling pathways crosstalk via the RAF-1/MST-2 interaction in malignant melanoma. Oncol Rep. 2017; 38(2):1199-1205. DOI: 10.3892/or.2017.5774. View

Markovic S, Erickson L, Rao R, Weenig R, Pockaj B, Bardia A . Malignant melanoma in the 21st century, part 1: epidemiology, risk factors, screening, prevention, and diagnosis. Mayo Clin Proc. 2007; 82(3):364-80. DOI: 10.4065/82.3.364. View

Avruch J, Khokhlatchev A, Kyriakis J, Luo Z, Tzivion G, Vavvas D . Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog Horm Res. 2001; 56:127-55. DOI: 10.1210/rp.56.1.127. View

Pan D . The hippo signaling pathway in development and cancer. Dev Cell. 2010; 19(4):491-505. PMC: 3124840. DOI: 10.1016/j.devcel.2010.09.011. View

Nallet-Staub F, Marsaud V, Li L, Gilbert C, Dodier S, Bataille V . Pro-invasive activity of the Hippo pathway effectors YAP and TAZ in cutaneous melanoma. J Invest Dermatol. 2013; 134(1):123-132. PMC: 3938155. DOI: 10.1038/jid.2013.319. View

Yu F, Zhao B, Guan K . Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell. 2015; 163(4):811-28. PMC: 4638384. DOI: 10.1016/j.cell.2015.10.044. View

Candido S, Rapisarda V, Marconi A, Malaponte G, Bevelacqua V, Gangemi P . Analysis of the B-RafV600E mutation in cutaneous melanoma patients with occupational sun exposure. Oncol Rep. 2014; 31(3):1079-82. PMC: 3926654. DOI: 10.3892/or.2014.2977. View

10.

Curtin J, Fridlyand J, Kageshita T, Patel H, Busam K, Kutzner H . Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353(20):2135-47. DOI: 10.1056/NEJMoa050092. View

11.

Bastian B . The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol. 2014; 9:239-71. PMC: 4831647. DOI: 10.1146/annurev-pathol-012513-104658. View

12.

Kim J, Lazar A, Davies M, Homsi J, Papadopoulos N, Hwu W . BRAF, NRAS and KIT sequencing analysis of spindle cell melanoma. J Cutan Pathol. 2012; 39(9):821-5. PMC: 3881367. DOI: 10.1111/j.1600-0560.2012.01950.x. View

13.

Dunn J, Watson M, Aitken J, Hyde M . Systematic review of psychosocial outcomes for patients with advanced melanoma. Psychooncology. 2016; 26(11):1722-1731. DOI: 10.1002/pon.4290. View

14.

Kasparian N, McLoone J, Butow P . Psychological responses and coping strategies among patients with malignant melanoma: a systematic review of the literature. Arch Dermatol. 2009; 145(12):1415-27. DOI: 10.1001/archdermatol.2009.308. View

15.

Dong C, Davis R, Flavell R . MAP kinases in the immune response. Annu Rev Immunol. 2002; 20:55-72. DOI: 10.1146/annurev.immunol.20.091301.131133. View

16.

Tacastacas J, Bray J, Cohen Y, Arbesman J, Kim J, Koon H . Update on primary mucosal melanoma. J Am Acad Dermatol. 2014; 71(2):366-75. DOI: 10.1016/j.jaad.2014.03.031. View

17.

Dankort D, Curley D, Cartlidge R, Nelson B, Karnezis A, Damsky Jr W . Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet. 2009; 41(5):544-52. PMC: 2705918. DOI: 10.1038/ng.356. View

18.

Dhomen N, Reis-Filho J, da Rocha Dias S, Hayward R, Savage K, Delmas V . Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009; 15(4):294-303. DOI: 10.1016/j.ccr.2009.02.022. View

19.

Lopez-Bergami P, Fitchman B, Ronai Z . Understanding signaling cascades in melanoma. Photochem Photobiol. 2007; 84(2):289-306. PMC: 2874067. DOI: 10.1111/j.1751-1097.2007.00254.x. View

20.

Pollock P, Harper U, Hansen K, Yudt L, Stark M, Robbins C . High frequency of BRAF mutations in nevi. Nat Genet. 2002; 33(1):19-20. DOI: 10.1038/ng1054. View