Tumor Lymphangiogenesis as a Potential Therapeutic Target

Table 3

Tumor lymphangiogenic transcription factors.

Transcription factors	Target genes	Association with cancer	References
PROX-1	Genes involved in proteolysis, lymphatic differentiation, cell adhesion, and migration	(i) Prox1 is strongly expressed by human Kaposi’s sarcoma (a neoplasm of KSHV-infected vascular endothelium). (*); (ii) Highly expressed Prox1 induces lymphatic reprogramming, more aggressive tumor growing, and local invasion.	[176, 177]
SOX18	Prox-1, VCAM-1, Claudin-5	(i) SOX18 plays a critical role in initial steps of tumor angiogenesis and subsequent induction of tumor growth.; (ii) SOX18 has also been found to express on tumor neolymphatics, suggest its potential role in regulation of tumor lymphangiogenesis.	[172, 178, 179] (unpublished data)
COUP-TFII	(i) Nrp2, coreceptor for VEGF-C; (ii) Suppress VEGFR-1 expression in ECs	(i) Essential factor for tumor-induced neo-lymphangiogenesis in spontaneous mouse breast cancer model; (ii) Control pancreatic islet tumor angiogenesis by regulating VEGF/VEGFR-2 signalling	[11, 180]
FOXC2	Integrin β3 subunit, Dll4, Hey2, CXCR4	(i) FOXC2 might regulate tumor angiogenesis by target genes including integrin β3, CXCR4, and Delta-like 4 (Dll4).; (ii) High FOXC2 expression (mRNA level) group showed a higher incidence of advanced tumor stage, lymph node metastasis, and lymphatic invasion in esophageal cancer patients.	[181, 182]

*KSHV: Kaposi’s sarcoma-associated herpesvirus (the involvement of lymphatic transcription factors—NFATc1 and Tbx1— in cancer metastasis has not been reported recently).