Table 1.

The role of signaling pathways in anchorage-independent survival and their implication in the treatment of cancer metastasis.

Active signaling pathway	Functions during detachment	Activated in cancer metastasis	Efficacy of targeting inhibitors in metastatic patient or animal
Integrin/FAK/SFKs pathway	Protecting cells from anoikis and activating protective autophagy	Activated in a variety of metastasis, including breast cancer, lung cancer, melanoma, colorectal cancer, prostate cancer, glioblastoma, liver cancer [96]	Melanoma [176], breast cancer [177], colorectal cancer [178], ovarian cancer [179], hepatocellular carcinoma [180], non-small cell lung cancer [181], etc.
Ras/ERK signaling pathway	Attenuating cellular stress and enhancing anoikis resistance	Colorectal cancer [132, 135], germ-cell tumors [136], multiple myeloma [137], skin cancer [138, 139], melanoma [140] and lung cancer [141]	Thyroid cancer [142, 143], non-small cell lung cancer [144, 182], melanoma [145, 183, 184], colorectal cancer [185], biliary tract cancer [186]
PI3K/ATK signaling pathway	Enhancing nutrients uptake, decreasing ROS production and inhibiting anoikis	Colorectal cancer [135, 146], melanoma [147, 148], prostate cancer [149], lung cancer, breast cancer and renal cell carcinomas [150]	Endometrial cancer [155], breast cancer [156, 187–189], gastric cancer [190], cervical carcinoma [191], prostate cancer [192, 193], non-small cell lung cancer [194] and other cancers [195, 196]
Rho signaling pathway	Regulating cytoskeleton reorganization and mechanical transduction, protecting cells from anoikis and entosis	Lymphoma [157], colorectal cancer [158, 159], breast cancer [197, 198], liver cancer [199, 200], melanoma [201, 202], pancreatic cancer [203]	Nasopharyngeal cancer [160], pancreatic cancer [161], breast cancer [204], melanoma and colorectal cancer [162]
Hippo signaling pathway	Regulating mechanical transduction, enhancing nutrients uptake, protecting from anoikis and autophagy	Breast cancer [165, 205, 206], prostate cancer [117], lung cancer [207], colorectal cancer [208], melanoma [165], gastric cancer [163]	Breast cancer [165, 209] and melanoma [165]