Table 1.

Klotho is a tumour suppressor of human malignancies.

Tumour Type	Unmet Clinical Need	Model Systems/ Tissue Analysis
Colorectal Cancer	3rd most common cancer and 2nd leading cause of mortality [9]. Five-year survival for stage IV remains lower than 10% [80].	Cell lines HCT116, H-29, SW480, Colo-320 [69] Orthotopic C57BL/6 mice using MC38 colorectal cancer cells [69] Azoxymethane induced polyps in C57BL/6 immune-competent mice [44] Decreased Klotho expression in colon cancer tissues [45]
Oesophageal and Gastric Cancer	Oesophageal cancer is 7th most common cancer and 6th in mortality. Gastric cancer is the 5th most common cancer and 3rd leading cause of cancer death [9].	Cell lines MKN28, MKN-45, AGS, GC-7901, GES-1, NCI-N87, SNU1, SNU16 [7,47] Decreased Klotho expression in OSCC [48] Klotho expressing OSCC associated with improved survival [48]
Pancreatic Cancer	Survival rates have remained relatively unchanged since the 1960s [81], and is frequently diagnosed at a late stage [82].	Panc1, MiaPaCa2, and Colo357 [73] Female athymic nude mice Panc1 xenograft models [83] Decreased Klotho expression in Pancreatic cancer biopsies
Breast Cancer	Breast cancer accounts for 30% of new cancer diagnosis in women [82,84].	Cell lines MCF-12A, MCF-7, MDA-MB-231, MDA-MB-436, SKBR3, T47D, BT-474 [49] Decreased Klotho expression in breast cancer tissues [49,67] Nude mice xenografts using MDA-MB-231 cells [68]
Lung Cancer	Most common cancer diagnosed in both gender groups and the leading cause of mortality [9].	Cell line A549 [85]
Ovarian Cancer	The 6th most common cancer in females usually diagnosed late with high fatality rate [86].	Cell lines A2780, SKOV-3, OVCA 432, OVCAR-5, OVCAR-8, CaOV3, CaOV4 [51] C57BL/6 mice xenografts using A2780 cells [51] Decreased Klotho expression in invasive disease [51] Klotho high expressing tumours associated with improved survival [51]
Thyroid Cancer	Most common endocrine malignancy [9]. Frequently affects young women below the age of 30 years.	Cell lines FTC133 and FTC238 [77] Klotho inhibits STC1 expression in thyroid cancer cells [77]
Melanoma	Rising incidence [82]. 5th most commonly diagnosed cancer.	Cell lines G361, UACC903 and M93-047 [76] Cell lines characterised according to their levels of Wnt-5A [76] Klotho is lost as cells become more metastatic and may regulate Wnt-5A, which is correlated with more advanced metastatic disease. [76]
Renal Cancer	Rising incidence. Five-year survival for patients with renal cell cancer is less than 10% [87].	Human RCC cell line 786-O, OS-RC-2, ACHN, Caki-1 [52]. Klotho expression blunts RCC cellular migration and invasion in vitro [52]. Soluble, as well as tissue Klotho levels progressively reduced in patients with advanced clear cell renal cell carcinoma [52].
Cervical Cancer	Second leading cause of cancer death in women aged 20–39 years [82].	Cell line C-33A, CaSki, HeLa, SiHa, SNU-17, SNU-703, SNU-1160, SNU 1299 [74] Loss of Klotho mRNA observed in several cell lines and invasive carcinoma samples but not during the early, preinvasive phase of primary cervical cancer [74].